Background Point-of-care (POC) international normalized ratio (INR) monitoring by healthcare professionals could eliminate the need for venous blood sampling in non-self-monitoring (NSM) patients on vitamin K antagonists (VKA). However, few studies have investigated the impact of POC INR monitoring on the quality of treatment in these patients and real-world data on this issue are lacking. Objectives To investigate the safety, efficacy and quality of anticoagulant control during POC INR monitoring as compared with laboratory INR monitoring in NSM patients. Methods We performed a retrospective cohort study using data from the anticoagulation clinic of the Star-Medical Diagnostic Center (Rotterdam, the Netherlands). Patients who received treatment with VKA between 29 May 2012 and 29 May 2014 were eligible. Percentage of time in therapeutic range (TTR) and incidence rates of major clinical events (all-cause mortality, hospitalization, major bleeding and ischemic stroke) were compared for the year before and year after introduction of POC monitoring. Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals for major clinical events between exposure groups. Results In total, 1973 patients during the 1-year laboratory-monitoring observation period and 1959 patients during the 1-year POC-monitoring observation period were included. Median TTR was significantly lower during POC monitoring (77.9%; 95% CI, 67.2-87.4) than during laboratory INR monitoring (81.0%; 95% CI, 71.1-90.5). Adjusted hazard ratios for major clinical events were all around unity. Conclusions Although associated with lower TTR, POC INR monitoring is a safe and effective alternative to laboratory INR monitoring in NSM patients on VKA.