What is known and Objective: Drug–drug interactions (DDIs) cause considerable morbidity and mortality worldwide and may lead to hospital admission. Sophisticated computerized drug information and monitoring systems, more recently established in many of the emerging economies, including Malaysia, are capturing useful information on prescribing. Our aim is to report on an investigation of potentially serious DDIs, using a university primary care–based system capturing prescription records from its primary care services.  Methods: We retrospectively collected data from two academic years over 20 months from computerized databases at the Universiti Sains Malaysia (USM) from users of the USM primary care services.  Results and Discussion: Three hundred and eighty-six DDI events were observed in a cohort of 208 exposed patients from a total of 23 733 patients, representing a 2-year period prevalence of 876·4 per 100 000 patients. Of the 208 exposed patients, 138 (66·3%) were exposed to one DDI event, 29 (13·9%) to two DDI events, 15 (7·2%) to three DDI events, 6 (2·9%) to four DDI events and 20 (9·6%) to more than five DDI events. Overall, an increasing mean number of episodes of DDIs was noted among exposed patients within the age category ≥70 years (P = 0·01), an increasing trend in the number of medications prescribed (P < 0·001) and an increasing trend in the number of long-term therapeutic groups (P < 0·001).  What is new and Conclusion: We describe the prevalence of clinically important DDIs in an emerging economy setting and identify the more common potentially serious DDIs. In line with the observations in developed economies, a higher number of episodes of DDIs were seen in patients aged ≥70 years and with more medications prescribed. The easiest method to reduce the frequency of DDIs is to reduce the number of medications prescribed. Therapeutic alternatives should be selected cautiously.