Background: A high number of vitamin K antagonist (VKA) users have a low proportion of time in therapeutic range (TTR) resulting in a high number of bleeding and thromboembolism events. Objective: Can the quality of anticoagulation be improved by dispensing VKAs via multidose drug dispensing (MDD). Method: A randomized controlled trial in the Netherlands. Patients who used VKAs, ≥65 years of age with a TTR <65% were eligible for inclusion. All oral drugs were dispensed via MDD. In MDD systems, all oral chronic medication intended for one dosing moment is packed in plastic disposable pouches. Controls received VKAs by manual dispensing. The difference in TTR between the 6 months after- and 6 months before the index date. A mixed-effects model with the intervention, TTR before the index date, MDD system at baseline as covariates, and pharmacy as random effect. A per-protocol analysis was performed with all patients who completed the study as intended. Results: One hundred and seventy-nine patients were included. Mean age was 80.0 (SD 6.9) years. Mean TTR during the study was 79.2 ± 18.0% in the intervention group and 72.5 ± 20.1% in the control group. The intervention resulted in a 5.6% (95% CI: 0.1-11.1) increase in TTR compared to the control group. Per-protocol analysis resulted in an 8.3% (95% CI: 0.99-15.61) increase in TTR compared to the control group. No differences in reduction were observed between the intervention and control group. Conclusion: The quality of anticoagulation can be improved with the use of MDD systems.