The aim of this study was to assess whether heart failure (HF) could be a risk factor for adverse drug reactions (ADRs) among hospitalized older adults. This study included 19,496 patients admitted to community- and university-based hospitals in Italy (mean age 70 +/- 14 years; 49.7% female). ADRs were identified in 207 of the 2,413 (8.6%) patients with HF and in 855 (5.0%) of the 17,083 patients without HF (P < 0.001). After adjusting for potential confounders, HF was shown to be associated with an increased likelihood of experiencing an ADR (odds ratio (OR) 1.29; 95% confidence interval (CI) 1.06-1.56). After stratifying the sample by gender, the association continued to be seen in the women (OR 1.58; 95% CI 1.22-2.05) but not in the men (OR 0.99; 95% CI 0.74-1.34). In conclusion, HF appears to be associated with a higher rate of ADRs among hospitalized patients. Gender may influence the effect of HF on the risk of ADRs.