OBJECTIVES: To identify patient characteristics associated with polypharmacy and inappropriate medication (PIM) use among older patients with newly diagnosed cancer. DESIGN: Cross-Sectional Study. SETTING: Ambulatory oncology clinics at an academic medical center. PARTICIPANTS: 117 patients aged ≥ 65 years with newly diagnosed histologically confirmed stage I-IV cancer were enrolled between April 2008 and September 2009. MEASUREMENTS: Medication review, included patient self-report and medical records. Polypharmacy was defined as the concurrent use of ≥ five medications, (Yes/No). PIM use was defined as use of ≥ one medication included in the 2003 update of Beers Criteria, (Yes/No). RESULTS: The prevalence of polypharmacy and PIM use were 80% and 41%, respectively. Three independent correlates of medication use were identified. An increase in comorbidity count by one, ECOG-PS score by one, and PIM use by one, was associated with an increase in medication use by 0.48 (P=0.0002), 0.79 (P=0.01) and 1.22 (P=0.006), respectively. Two independent correlates of PIM use were identified. The odds of using PIMs decreased by 10% for one unit increase in Body Mass Index [Odds Ratio (OR) 0.90, 95% CI = (0.84, 0.97)], and increased by 18% for each increase in medication count by one [OR 1.18, 95% CI = (1.04, 1.34)]. CONCLUSION: There was a high prevalence of polypharmacy and PIM use in older patients with newly diagnosed cancer. Given the co-occurrence of polypharmacy with poor performance status and multi-morbidity, multi-dimensional interventions are needed in the geriatric-oncology population to improve health and cancer outcomes.