OBJECTIVES:  Polypharmacy among individuals with cancer is an alarming issue. We aimed to determine the rates of polypharmacy and predictors among cancer survivors in the United States. METHODS:  This cross-sectional analysis included responses to survey questions collected as part of the Medical Expenditures Panel Survey (MEPS) for the survey years 2008, 2010, 2012, and 2014. The total number of prescriptions per person/household response were determined by picking the panel with the most reported medications. Polypharmacy was defined as having five or more classes of medications. We chose to include only those cancer survivors who had a single tumor. Descriptive statistics were used to determine significant differences in characteristics among those with and without polypharmacy, and logistic regression was employed to identify predictors of polypharmacy in a multivariate framework. RESULTS:  An estimated 46.5 million cancer survivors cumulative for the four years comprised our study sample. Of these, 49.3% met our definition of polypharmacy while 50.7% had four classes of medications or less. Older age (65+ vs. 18-39, adjusted odds ratio (AOR)= 1.62, confidence interval (CI): 1.15-2.29), female gender (AOR= 0.75, CI: 0.59-0.95), number of chronic conditions (1 vs none, AOR= 2.26, CI: 1.83-2.80 and 2+ vs none, AOR= 8.28 CI: 6.63-10.35), and increased number of total visits (10 to 19 visits compared to 0 to 4, AOR= 1.82, CI: 1.44-2.30 and 20+ visits compared to 0 to 4, AOR= 3.59 CI: 2.72-4.74) were significant predictors of polypharmacy. CONCLUSIONS: Polypharmacy is highly prevalent among cancer survivors in the United States, suggesting greater surveillance of adverse drug interactions among this vulnerable group.