Importance: Despite concern about harms related to long-term prescribed opioid use among individuals with chronic noncancer pain (CNCP), no study has examined whether the same patients engage in a risky pattern of use consistently for the long term. Objective: To examine the prevalence, incidence, persistence, and cessation of a range of opioid behaviors, indicators of extramedical use, and harm among individuals who are prescribed opioids. Design, Setting, and Participants: This 5-year prospective cohort study in communities across Australia included 1514 adults who were prescribed opioids for CNCP. Data collection took place from August 2012 to December 2018, and data analysis took place from February to November 2020. Exposure: Prescription opioid use. Main Outcomes and Measures: High-dose opioid use (≥200 oral morphine equivalent [OME] mg/d); requesting an increase in opioid dose; requesting an early prescription renewal; tampering with opioid medication; diversion of medication to others; and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision opioid dependence. Cessation of opioid use was also assessed. Results: Of the 1514 participants, 672 (44.39%) were men, the mean (SD) age was 58 (19) years, and 737 (48.68%) were unemployed. At each annual interview, approximately 1 in 8 people (10.98% [95% CI, 10.33%-11.63%] to 14.73% [95% CI, 13.98%-15.48%] at any given interview) were taking more than 200 OME mg/d; comparatively more had requested an increased dosage in the previous 3 months (8.46% [95% CI, 7.89%-9.03%] to 23.77% [95% CI, 22.82%-24.73%]); and fewer asked for an early prescription renewal (4.61% [95% CI, 4.19%-5.03%] to 13.97% [95% CI, 13.24%-14.70%]). In any given interview, between 3.06% (95% CI, 2.72%-3.40%) and 7.86% (95% CI, 7.31%-8.41%) of respondents reported tampering and between 0.47% (95% CI, 0.33%-0.60%) and 1.39% (95% CI, 1.16%-1.62%) reported diversion to others. Between 8.28% (95% CI, 7.71%-8.84%) and 13.06% (95% CI, 12.35%-13.77%) met criteria for opioid dependence at each interview. Opioid cessation increased across interviews, from year 1 (9.15% [95% CI, 8.55%-9.74%]) to year 5 (20.02% [19.14%-20.89%]). There was considerable incidence and cessation in all behaviors from 1 interview to the next: most who engaged in any of these behaviors only did so at only 1 interview. For pharmaceutical opioid dependence, between 55.26% (95% CI, 53.81%-56.71%) and 64.44% (95% CI, 62.87%-66.00%) of cases in 1 interview did not meet dependence criteria in the following interview. Conclusions and Relevance: These findings suggest considerable fluidity in opioid use, extramedical behaviors, and opioid dependence among people with CNCP. This reinforces the need for reassessment of the effectiveness and safety of prescription opioid use over time. © 2021 American Medical Association. All rights reserved.