AbstractObjective.Polypharmacy has been associated with morbidity and mortality in patients with cancer. Data about polypharmacy among patients with ovarian cancer are limited. The primary objective of this study was to evaluate polypharmacy in a cohort of patients with ovarian cancer and to assess the evolution of polypharmacy from initial presentation to 2 years posttreatment. A secondary objective was to evaluate differences in polypharmacy between a subset of patients primarily treated in our comprehensive cancer center (CCC) and our safety net hospital (SNH).Methods.Women treated for ovarian cancer between January 1, 2011, and December 31, 2016, were included. Data were abstracted from the electronic medical record. Medication safety was assessed using the established Anticholinergic Burden (ACB) scale and the Beers criteria. Statistical analyses were performed using paired t tests and Cox proportional hazards models, with significance set at p < .05.Results.The study included 152 patients. The majority of patients had high‐grade serous carcinoma. Hypertension was the most common medical problem. The mean number of medications at the time of diagnosis was 3.72. Paired testing demonstrated significant patient‐level increases in the number medications at 2 years following initial diagnosis (4.16 vs. 7.01, p < .001). At the CCC, 47.4% of patients met criteria for polypharmacy at diagnosis compared with 19.4% at the SNH (p < .001). By 2 years postdiagnosis, 77.6% of patients at the CCC met criteria for polypharmacy compared with 43.3% at the SNH (p = .001). The use of any medications on the ACB scale (p < .001) increased significantly between initial diagnosis and 2 years for the entire population. Polypharmacy was not a significant predictor of overall survival.Conclusion.Polypharmacy worsens as women go through ovarian cancer treatment. Both at initial presentation and at 2 years postdiagnosis, rates of polypharmacy were higher at the CCC. Polypharmacy did not have an effect on survival in this cohort.Implications for Practice.Awareness of escalating numbers of medications and potentially adverse interactions is crucial among women with ovarian cancer, who are at high risk for polypharmacy.