Patients undergoing hematopoietic stem cell transplantation (HSCT) are at risk of developing potential drug-drug interactions (PDDIs). The aim of this study was to assess the prevalence of PDDIs that occur in HSCT patients on the day of hematopoietic stem cell infusion. We performed a cross-sectional study based on the evaluation of prescriptions to HSCT patients on the day of infusion (day 0). The PDDIs were analyzed using the DRUG-REAX(®) system and classified according to the severity level, available scientific evidence, time of onset, and potential clinical impact. Forty patients undergoing HSCT were included in this study; 33 patients (82.5%) were exposed to at least one major and one contraindicated PDDI in a concomitant manner. All patients exposed to PDDIs had an increased risk of cardiotoxicity. Most cases of PDDIs were classified as being of major severity (80.9%), with time of onset not specified (61.9%), and with good or excellent scientific evidence (52.4%). HSCT patients have a high prevalence of clinically significant PDDIs. The management of PDDIs requires an approach that includes biochemical tests, installation of cardiac monitors, periodic electrocardiograms, implementation of electronic prescriptions with a PDDI alert system, and availability of the PDDI databases.