Background: Patients with metastatic BC have a high incidence of bone metastasis with associated morbidity and mortality. OIs including denosumab and zoledronic acid reduce the rate of skeletal-related events (SREs). Since denosumab was approved in 2011, there have been no analyses about the comparative effectiveness and safety of denosumab versus zoledronic acid. Methods: Patients with BC treated with three or more doses of either denosumab or zoledronic acid after 2011 were identified in Stanford’s BC research database, Oncoshare. SREs were defined as a composite measure of spinal cord compression, pathologic fracture, surgery or radiation to bone. Unadjusted Cox proportional hazard models were fit to time to: first SRE, subsequent SRE, overall survival (OS) and BC-specific survival. Results: 515 patients were identified: 388 and 127 treated with denosumab and zoledronic acid per oncologist’s discretion, respectively. Groups were well balanced for age at diagnosis, race/ethnicity, tumor grade, prior chemotherapy use and median time from first OI therapy to last follow-up. More patients with triple-negative BC (TNBC) received zoledronic acid. Median follow-up time from first OI dose was 28 months. 42% of patients experienced at least one SRE and there were no differences in incidence of first or subsequent SREs between groups (Table). Median OS was 91 months with no statistically significant difference between groups. Median BC-specific survival was not reached (78% of patients survived), however, patients in the zoledronic acid group had over twice the risk of BC-specific mortality, a difference that remained significant after adjustment for TNBC status. There was no difference in adverse events including osteonecrosis of the jaw, vertebral fracture or hypocalcemia. Conclusions: In a contemporary, real-world care setting, we observed no difference in the incidence of SREs or OS between metastatic BC patients treated with denosumab or zoledronic acid.