Background: Home care (HC) patients are characterized by a high level of complexity, which is reflected by the prevalence of multimorbidity and the correlated high drug consumption. This study assesses prevalence and factors associated with polypharmacy in a sample of HC patients in Europe. Methods: We conducted a cross-sectional analysis on 1873 HC patients from six European countries participating in the Identifying best practices for care-dependent elderly by Benchmarking Costs and outcomes of community care (IBenC) project. Data were collected using the interResident Assessment Instrument (interRAI) instrument for HC. Polypharmacy status was categorized into three groups: non-polypharmacy (0–4 drugs), polypharmacy (5–9 drugs), and excessive polypharmacy (≥ 10 drugs). Multinomial logistic regressions were used to identify variables associated with polypharmacy and excessive polypharmacy. Results: Polypharmacy was observed in 730 (39.0%) HC patients and excessive polypharmacy in 433 (23.1%). As compared with non-polypharmacy, excessive polypharmacy was directly associated with chronic disease but also with female sex (odds ratio [OR] 1.58; 95% confidence interval [CI] 1.17–2.13), pain (OR 1.51; 95% CI 1.15–1.98), dyspnea (OR 1.37; 95% CI 1.01–1.89), and falls (OR 1.55; 95% CI 1.01–2.40). An inverse association with excessive polypharmacy was shown for age (OR 0.69; 95% CI 0.56–0.83). Conclusions: Polypharmacy and excessive polypharmacy are common among HC patients in Europe. Factors associated with polypharmacy status include not only co-morbidity but also specific symptoms and age.