Background: Self-administered medication (SAM) is encouraged in many hospitals worldwide as it increases patients’ knowledge and understanding of their medication, but the effects on other outcomes, e.g. compliance or medication errors, were unclear. Objectives: To compare medication knowledge, adherence, medication errors, and hospital readmission among inpatients receiving SAM education under the supervision of a multidisciplinary team (study group) with those receiving routine nurse-administered medication (control group). Methods: This study was a PROBE design. Inpatients with chronic diseases were randomly allocated (1:1) to either the study group or the control group using stratified-block randomization. Knowledge of medications was measured at hospital discharge and at the first two follow-up visits; adherence was measured at the first two follow-up visits, medication errors while in hospital, and hospital readmission within 60 days after discharge. For normally distributed continuous outcomes, mean difference and 95%CI were estimated; otherwise the median and the Mann-Whitney test p-value were reported. The percentage difference and 95%CI were reported for binary outcomes. Results: 70 patients were randomized (35 in each group); all received complete follow-up. Both groups were similar at baseline. Mean (SD) age (years) were 59.2 (11.0) for the study group and 58.3 (12.0) for the control group. Percentages of females in the respective groups were 54.3 and 60.0. Mean time from discharge to the first follow-up visit was two weeks in both groups and time to the second follow-up visit were 68.8 days (study group) and 55.0 days (control group). The study group had significantly higher medication knowledge than the control group at hospital discharge (of the 10-point scale, medians, 8.56 and 6.18, respectively, p<0.001). The corresponding figures were similar in both groups at the first follow-up visit (medians, 8.25 and 6.26, respectively, p<0.001). Adherence to medication at the first visit in the study group (percentage mean 92.50% (SD=5.33%)) was significantly higher than that in the control group (79.60% (SD=5.96%)), percentage mean difference 12.90%, [95%CI 10.20%:15.60%], p<0.001. Medication knowledge and adherence were sustained at the second follow-up visit. During hospitalization, no medication errors were found in the study group, and minimal errors occurred in the control group (1.48%, [95%CI 0.68%:2.28%] of doses administered, p=0.001). Hospital readmission within 60 days after discharge was significantly lower in the study group (11.4%) than that in the control group (31.4%), percentage difference 20.0% (95%CI 1.4%:38.6%), 1-side Fisher exact p=0.039. Conclusions: Among in-patients with chronic diseases, SAM program significantly increased knowledge of and adherence to prescribed medications. Medication errors regarding administration errors were infrequent but significantly higher in the control group. SAM reduced hospital readmission within 60 after discharge.