AIMS: Falling in older persons is a frequent and serious clinical problem. Several drugs have been associated with increased fall risk. The objective of this study was to identify differences in the incidence of falls after withdrawal (discontinuation or dose reduction) of fall-risk-increasing drugs as a single intervention in older fallers. METHODS: In a prospective cohort study of geriatric outpatients, we included 139 patients presenting with one or more falls during the previous year. Fall-risk-increasing drugs were withdrawn, if possible. The incidence of falls was assessed within 2 months of follow-up after a set 1 month period of drug withdrawal. Multivariate adjustment for potential confounders was performed with a Cox proportional hazards model. RESULTS: In 67 patients, we were able to discontinue a fall-risk-increasing drug, and in eight patients to reduce its dose. The total number of fall incidents during follow-up was significantly lower in these 75 patients, than in those who continued treatment (mean number of falls: 0.3 vs. 3.6; P value 0.025). The hazard ratio of a fall during follow-up was 0.48 (95% confidence interval (CI) 0.23, 0.99) for overall drug withdrawal, 0.35 (95% CI 0.15, 0.82) for cardiovascular drug withdrawal and 0.56 (95% CI 0.23, 1.38) for psychotropic drug withdrawal, after adjustment for age, gender, use of fall-risk-increasing drugs, baseline falls frequency, comorbidity, Mini-Mental State Examination score, and reason for referral. CONCLUSIONS: Withdrawal of fall-risk-increasing drugs appears to be effective as a single intervention for falls prevention in a geriatric outpatient setting. The effect was greatest for withdrawal of cardiovascular drugs.