BACKGROUND Self-administration of medication (SAM) during hospitalization is a complex intervention where patients are involved in their course of treatment. The study aim was to pilot test the SAM intervention. The objectives were to assess the feasibility of conducting a randomized controlled trial on the safety and cost-consequences of SAM during hospitalization. METHODS The study was performed in a Danish cardiology unit.Patients ≥ 18 years capable of self-administering medication during hospitalization were eligible. Patients were excluded if they did not self-administer medication at home, were incapable of self-administering medication, were not prescribed medication suitable for self-administration, did not bring their medication, or were unable to speak Danish.Feasibility was assessed as part of the pilot study. A future randomized controlled trial was considered feasible if it was possible to recruit 60 patients within 3 months, if outcome measurement method was capable of detecting dispensing errors in both groups, and if patients in the intervention group were more satisfied with the medication management during hospitalization compared to the control group.Forty patients were recruited to gain experience about the intervention (self-administration). Additionally, 20 patients were randomized to the intervention or control group (nurse-led dispensing) to gain experience about the randomization procedure.Dispensing error proportions were based on data collected through disguised observation of patients and nurses during dispensing. The error proportion in the control group was used for the sample size calculation. Patient acceptability was assessed through telephone calls. RESULTS Of the 60 patients recruited, one withdrew and 11 were discharged before observation resulting in analysis of 39 patients in the intervention group and nine in the control group. A dispensing error proportion of 3.4% was found in the intervention group and 16.1% in the control group. A total of 91.7% of patients in the intervention group and 66.7% in the control group were highly satisfied with the medication management during hospitalization. The overall protocol worked as planned. Minor changes in exclusion criteria, intervention, and outcome measures were considered. CONCLUSIONS It may be feasible to perform a pragmatic randomized controlled trial of the safety and cost-consequences of self-administration of medication during hospitalization. BACKGROUND ClinicalTrials.gov, NCT03541421, retrospectively registered on 30 May 2018.