PURPOSE: Women receiving aromatase inhibitors (AIs) for breast cancer frequently experience musculoskeletal symptoms (AIMS) including joint pain, stiffness, and muscle weakness. Aerobic exercise may reduce AIMS, but the evidence is inconclusive. This investigation examined whether aerobic exercise reduces pain in women with breast cancer. METHODS: Pain was a secondary outcome of a randomized controlled trial where postmenopausal women with breast cancer receiving AIs (N = 136) with or without pain were randomized to 6 months of moderate-intensity aerobic exercise (n = 70) or usual care (n = 66). The primary (Brief Pain Inventory severity, interference and worst pain) and secondary (SF-36 Bodily Pain and Breast Cancer Prevention Trial Symptom Checklist Musculoskeletal Pain) pain outcomes were assessed at pre-randomization (T1) and post-intervention (T2). Linear mixed modeling with linear contrasts was used to examine the effect of group assignment on outcomes. RESULTS: Participants were a median = 4.7 months post-breast cancer diagnosis at T1. Group-by-time interactions were observed for pain severity ( CONCLUSION: Our results suggest that aerobic exercise prevents pain increase and may reduce pain prevalence when initiated early in AI therapy. The trial was registered at Clinical Trials.gov (NCT02793921) on May 20, 2016. KEY FINDINGS: Moderate-intensity aerobic exercise may prevent increases in pain and reduce pain when initiated early in AI therapy in postmenopausal women with breast cancer. Lack of exercise may be associated with increased over-the-counter pain medication use.