OBJECTIVE: To investigate the occurrence of all drug-related problems (DRPs) amongst hospitalised patients on polypharmacy, and to confirm the association of advanced age and the female gender with adverse drug reactions (ADRs). METHODS: A retrospective, cross-sectional study was carried out in patients on polypharmacy (5 and more drugs). Chi-square test was used to test for significant differences (p <0.05) between the age and gender of patients, and their risk of developing DRPs. A two-tailed, unpaired t-test was employed to test for significant difference (p <0.05) between the number of medications taken and the risk of DRPs. Relative risk (RR) analysis was performed for geriatric (patients above 65 years old) and female patients to assess their propensity in developing ADRs. RESULTS: The study population consisted of 347 patients (43% female), aged 16 - 97 (average 66 years). Geriatrics made up 58.2% of this population. The number of medications per patient ranged from 5 to 14 (mean 7.4 ± 2.1). The types of DRPs identified included: inappropriate treatment (42.9%); potential drug interactions (45.0%); inappropriate dosages (20.7%); unsafe drugs for patients (13.5%); ADRs (7.5%). There were no statistical correlations when age and gender were compared between patients with and without DRPs. However, number of medications taken was a risk factor for the presence of DRPs (p = 0.001). RR for geriatrics and female patients to develop ADRs are found to be 1.01 (95% CI: 0.52, 1.85) and 0.79 (95% CI: 0.40, 1.55), respectively. CONCLUSION: Our results established that DRPs in hospitalised patients on polypharmacy in Singapore is comparable to that in other developed countries. Our results also support that polypharmacy is a greater risk factor than age where high susceptibility for DRPs, especially ADRs is concerned. The low RR of geriatrics and female patients developing ADRs deviates from published results and may be confounded by our inclusion criteria.