An intervention, SelfMED, was introduced to facilitate patient self-management of medication during hospitalization. This study aimed to evaluate the feasibility and safety of the SelfMED intervention. All patients in a cardiology ward in a Belgian regional hospital were assessed for suitability for inclusion, applying an evidence-based stepped assessment tool. Patients eligible for medication self-management and willing to participate were included in the study (i.e., consecutive sampling). Patients who self-managed their medication were closely monitored by nurses. The feasibility of medication self-management was evaluated by implementation and completion rates and the opinions of cardiologists. Safety was evaluated by medication administration errors and errors in patients' registration of intake. Of 159 patients assessed for eligibility to self-manage medication in-hospital, 61 were included. A total of 367 medicines were self-managed. Pill counts showed 3 administration errors (0.8%), and on 6 occasions (1.7%) the patient's registration of the intake was incorrect. SelfMED was deemed feasible within the hospital ward. In cardiologists' opinions, SelfMED requires substantial time investment. In summary, SelfMED facilitated patient medication self-management in-hospital. As an essential step in the preparation for a full trial, this study showed it is feasible and safe to implement the intervention and identified some possibilities for refinement.