Background: he number of patients on warfarin therapy is rising steadily. Although warfarin is beneficial, it carries a high risk of bleeding, especially if the international normalized ratio (INR) values exceed 3.0. Currently, no warfarin initiation regimens have been developed for the Asian population, especially for Malaysians. Objective: This article describes the efficacy and safety of a new initiation regimen for warfarin among warfarin-naive patients. Method: Data were retrospectively collected from the ambulatory and inpatient settings. Results: A total of 165 patients who each had a target INR of 2.0 to 3.0 were included in the study. The mean age was 57.2 years and 94 patients were male. A total of 108 patients used Regimen 1 (5 mg/5 mg/3mg) and the rest of the patients used Regimen 2 (5 mg/3 mg/3 mg). Most patients used warfarin either for atrial fibrillation (52.1%) or for venous thromboembolism (29.7%). Overall, 88 of the patients had INR values above 50% from the baseline on Day 4. Additionally, 13 patients had INR values of >3.2, which required withholding and lower dose of warfarin. The predicted weekly maintenance warfarin dose (23 ± 0.5 mg/week) was found to have correlated closely with the actual maintenance dose (22.8 ± 0.5 mg/week; r 2 = 0.75). Nearly two thirds (70.3%) of the patients achieved the target INR on Day 11. Conclusion: The warfarin initiation regimens in this study was simple, safe, and suitable to be used in both ambulatory and inpatient settings for managing warfarin therapy.