To identify and compare the prevalence of drug-drug interactions (DDIs) in the intensive cardiac care units (CCUs) of 2 tertiary care hospitals and analyze their association with various predictors. Methods: This one-year prospective cross-sectional study was conducted in 2 tertiary care hospitals of Peshawar, Khyber Teaching Hospital (KTH) and Hayatabad Medical Complex (HMC), Peshawar, Pakistan, between January 2014 to Janury 2015. The patient medication profiles from the respective CCUs were evaluated for potential DDIs (PDDIs) using Micromedex DrugReax and Drug interaction facts. Results: The prevalence of PDDIs was 96.5% and 95.7% in the 2 hospitals, with over 1200 PDDIs in total. A significant association was found between the number of prescribed drugs and PDDIs in both hospitals. Conclusion: The knowledge of PDDIs is either lacking among the clinicians or is not taken into consideration. Monitoring PDDIs and timely interventions are required to minimize the adverse outcomes.