To explore healthcare professionals’ perceptions of challenges to chronic pain management. Qualitative interview study. Semistructured telephone interviews with healthcare professionals involved in chronic pain management and thematic analysis of transcriptions. Respondents (N = 16) described multiple challenges to chronic pain management: Management occurs in a complex care context complicated by the multidimensional, subjective nature of pain. A lack of systematic approaches fosters variation in care, and clinicians lack time and resources to manage pain holistically. Efforts to date have focused primarily on opioid reduction versus strategic approaches to manage chronic pain across the system. Comprehensive approaches to identify and manage chronic pain are nascent and, typically, narrowly focused on reducing opioid use. Respondents, however, recognized the importance of effective systematic management across inpatient and outpatient settings. These findings underscore the need to consider chronic pain as a chronic condition that warrants coordinated approaches to care such as standardized assessments; consistent, patient-centered outcome measures; and multimodal treatments that target both physical relief and underlying psychosocial factors. Reported barriers to chronic pain management included a complex, variable care context; the multidimensional, subjective nature of pain; variation in approaches to pain; and limited resources to manage pain holistically. Most chronic pain management focuses on opioid reduction versus strategic management across the system. Non–cancer-related chronic pain is a significant problem for many Americans. In 2016, 50 million US adults (20.4%) reported experiencing daily pain in the previous 6 months and nearly 20 million (8%) reported pain that limits daily activities. Use of opioids to relieve pain is pervasive. The 2015 National Survey on Drug Use and Health reported that 37.8% of noninstitutionalized US adults used prescription opioids, 4.7% misused them, and 0.8% had a use disorder. The most common reason for misuse, reported by 63.4%, was physical pain relief. However, opioids may have limited effectiveness for relieving chronic pain and may have significant adverse effects. Given the broad scope of chronic pain and opioid abuse, developing multimodal solutions that provide effective chronic pain management based on pathophysiology is an increasingly important health priority. However, nonopioid pain relief approaches may be underutilized. Studies report limited provider confidence in managing pain and limited knowledge about use of opioids for chronic pain. We conducted a qualitative interview study to understand healthcare professionals’ perceptions of challenges, gaps, and opportunities in chronic pain management. Using email and telephone contacts, we recruited participants from health systems taking part in Premier quality improvement initiatives. We identified stakeholders with interest and experience in chronic pain management who were from both larger and smaller hospitals across the United States (purposive sampling). We included a range of perspectives (physicians, nurses, quality improvement personnel, pharmacists) to ensure broad representation and promote generalizability of findings. Participants did not receive compensation or incentives for participation. Pfizer funded the study; Pfizer personnel did not participate in interviews and had no input into data analysis. The Advarra institutional review board approved the project as exempt research (Pro00028336). We conducted semistructured telephone interviews with healthcare professionals involved directly or indirectly in caring for patients with chronic pain to understand perceptions related to nonopioid pain management. We created an interview guide based on literature review and clinical practice experience. One of 2 members of the project team (C.P., N.A.S.) conducted each interview; all interviews were recorded (with participant consent) for further analysis. We conducted an inductive thematic analysis (content analysis) of interview data to understand respondents’ experiences in managing patients’ chronic pain and to identify themes. Team members (C.P., R.C., N.A.S.) coded and discussed an initial interview transcript to ensure alignment in approaches and preliminary codes. Two team members (C.P., N.A.S.) independently read and coded each transcript, assigning relevant codes using NVivo 12 software (QSR International, Melbourne, Australia). We developed the coding structure using pragmatic approaches, combining both bottom-up elements—developing codes from ideas and issues inherent in the data—and top-down elements, with issue identification informed by the a priori interview structure. We maintained an iterative codebook to record codes and operational definitions, and the team discussed differences to reach consensus on a final coding framework. Interviews (each approximately 40-60 minutes) were completed with 16 healthcare professionals who self-identified as being engaged in chronic pain management, from either a prescriber or nonprescriber perspective ( Figure ). Across interviews, respondents described complex contexts surrounding chronic pain treatment. Chronic pain management is complicated by the multifaceted nature of pain, the complex presentation of physical or mental health comorbidities and acute and chronic pain, multiple health system touchpoints, and consequences of opioid overuse and misuse. We describe challenges under system, pain management, provider, and patient domains. Details and quotes supporting each challenge appear in the available at ajmc.com ).