BACKGROUND: Patients with cancer-related pain are underrepresented in the opioid literature despite high opioid exposure and numerous risk factors for adverse opioid outcomes, including unnecessary persistent opioid use. The objective of this study was to determine the extent, historical trends, and predictors of new-onset persistent opioid use among older adult women after active breast cancer treatment. METHODS: Using Surveillance, Epidemiology, and End Results-Medicare data for opioid-naive women diagnosed with stage 0 to III breast cancer at the age of 66 to 90 years between 2008 and 2013, this study estimated overall and quarterly adjusted probabilities of new-onset persistent opioid use, which was defined as receiving ≥90 days' supply of opioids in the year after active breast cancer treatment. Sensitivity analyses were conducted with an alternative definition of persistent opioid use: any opioid fill 90 to 180 days after active cancer treatment. RESULTS: Nearly two-thirds of the subjects received prescription opioid therapy during cancer treatment. Quarterly probabilities of new-onset persistent opioid use after active treatment ranged from 2% to 4%; in sensitivity analyses, the alternative outcome definition resulted in predicted probabilities ranging from 11.4% to 14.7%. Subjects with more advanced disease, a higher comorbidity burden, a low-income status, and greater opioid exposure during active cancer treatment were more likely to develop persistent opioid use. CONCLUSIONS: Persistent opioid use was an infrequent occurrence among older adult patients with breast cancer completing cancer treatment between 2008 and 2013. This finding was encouraging because of the concerning opioid trends seen in noncancer populations. However, opportunities to further mitigate unsafe opioid use as a complication of cancer care, including standardization of persistent opioid use definitions, should be explored. Cancer 2020;126:814-822.