Summary Purpose:  To estimate the prevalence of potentially severe drug–drug interactions (DDIs) and their relationship with age, sex and number of prescribed drugs. Methods:  We analysed all prescriptions dispensed from 1 January 2003 to 31 December 2003 to individuals aged 65 or more registered under the Local Health Authority of Lecco, a northern Italian province with a population of almost 330 000 persons. Elderly who received at least two co‐administered prescriptions were selected to assess the presence of DDIs. Results:  The prevalence of potentially severe DDIs was 16%, and rose with increasing patient’s age and number of drugs prescribed. At multivariate analysis, the adjusted odds ratios rose from 1·07 (95% CI 1·03–1·11) in patients aged 70–74 to 1·52 (95% CI 1·46–1·60) in those aged 85 or older. Elderly taking more than five drugs on a chronic basis had a statistically significant higher risk of sever DDIs than those receiving less than 3 or 3–5 such drugs. Conclusions:  The elderly constitutes a population at high risk of DDIs. As physicians still have some difficulty in managing this problem, it is essential to highlight for them, which factors raise the risk of DDIs.