Background: Ramadan fasting presents unique challenges for patients with mechanical prosthetic heart valves on Warfarin therapy. This study aimed to evaluate the potential effects of Ramadan fasting and lifestyle changes during Ramadan on the INR level in patients using Vitamin K anticoagulant VKA (Warfarin) for mechanical prosthetic heart valves as anticoagulation. Methods: This prospective study included 150 Muslim patients with mechanical prosthetic heart valves, tracking their INR levels over a period encompassing the month of Ramadan. Patients underwent regular assessments, including clinical examinations, INR measurements, and echocardiography. Data were collected on medication regimens, Warfarin intake timing, and fasting adherence. Results: The mean INR levels increased during Ramadan, with the most significant rise occurring in the last two weeks. Patients exhibited a significantly higher mean INR during Ramadan compared to the pre-Ramadan and post-Ramadan periods. Importantly, more patients reached the supra-therapeutic INR range during Ramadan, while fewer were within the sub-therapeutic range when compared to the post-Ramadan phase. Conclusion: Ramadan fasting can lead to significant fluctuations in INR levels in patients with mechanical prosthetic heart valves using Warfarin. Careful monitoring and adjustment of anticoagulation therapy may be necessary to maintain therapeutic INR ranges during this religious observance.