Background Cardiovascular diseases are one of the major causes of mortality at the global level. They account for approximately 17.9 million deaths per year. Warfarin and acenocoumarol are the commonly used oral anticoagulants to treat and prevent thromboembolic disorders in patients with cardiovascular diseases. In India, approximately 2–2.5 million patients with rheumatic heart disease are receiving oral anticoagulation therapy. Additionally, this therapy is provided for stroke prevention in the case of atrial fibrillation and the treatment of valvular heart disease, stroke, and deep vein thrombosis. As the therapeutic range of these drugs is narrow and is affected by many factors, their use is challenging. This study aims to evaluate the effectiveness of a nursing intervention module in terms of adherence to therapy, knowledge, quality of life, and complications among patients receiving oral anticoagulation therapy. Furthermore, this study will address factors that affect adherence and the risk for bleeding by using a randomized controlled trial design. Methods This single-blind, single-center, randomized controlled trial will focus on adherence to oral anticoagulation therapy. A total of 320 patients who are on oral anticoagulation therapy will be randomized into blocks and allocated to either the intervention or standard care group. The intervention will comprise the use of a nursing intervention module that includes a booklet, log sheet, and decision aid on oral anticoagulation therapy adherence. Outcome measures, that is, knowledge regarding oral anticoagulation therapy, adherence, complications, and quality of life, will be assessed at the baseline and during follow-ups. Discussion Patient safety can be best achieved through patients’ adherence to medication dose and monitoring of blood test values. Thromboembolic and bleeding complications are likely to occur when either the patient does not adhere to the treatment or the therapeutic range of the international normalized ratio is not maintained. This study will assess the nonadherence behavior and the effectiveness of a nursing intervention module toward adherence behavior. Trial Registration This research project is registered under the Clinical Trial Registry of India (CTRI/2019/06/019610).