OBJECTIVES:  Opioids could be used effectively as a pharmacotherapy for severe cases of Adjuvant Endocrine Therapy (AET)-associated musculoskeletal and joint pain. This study explored differences in opioid use across different AET regimens, factors associated with opioid use, and the impact of opioid use on overall survival in female breast cancer patients treated with AET. METHODS:  We retrospectively analyzed 2006-2012 SEER-Medicare datasets, following patients for at least two years from the index date, defined as the first date they filled an AET prescription. The study included 10,773 Medicare-enrolled (Parts A, B, D) adult women with incident, primary, hormone-receptor-positive, stage I-III breast cancer. They were also required to be first-time AET users, alive for at least two years following AET initiation. The main independent variable in multivariate Cox-proportional hazard regression models was the AET regimen. The regimens included in this study were tamoxifen only, aromatase inhibitor(AI) only, AI switching to tamoxifen and vice versa, and mixed groups. We measured whether patients used opioids during follow-up and opioid use for at least 90 days during follow-up. RESULTS:  The results of the causal effects after applying for inverse probability treatment weights among AET regimens showed that the opioid use probabilities for those using tamoxifen only and AI only were similar (56.0% vs. 56.1%, respectively); the opioid use probabilities for those who switched from AI to TAM were higher than those for the tamoxifen-only and AI-only groups. Opioid use was also significantly (p<0.05) associated with AET non-adherence. Additionally, opioid users and chronic opioid users had significantly higher risks of death (adjusted hazard ratio [HR] = 1.63 and 1.41,P<0.05, respectively). CONCLUSIONS:  These findings suggest AET-induced pain, especially AI, may be an important indicator for drug switching and AET nonadherence. Managing AET side effects, especially pain, is integral to achieving better survival and quality of life outcomes in this population.