This quasi-experimental pre–post interventional study evaluated the effect of a structured health education program on patients’ knowledge and practice related to warfarin therapy in River Nile State, Sudan, during 2024–2025. Adult outpatients receiving warfarin for at least one month were enrolled using consecutive sampling and assessed before and after the intervention. A total of 150 participants completed both assessments. Data were collected using a structured interviewer-administered questionnaire covering key knowledge domains (indications, adherence, drug and food interactions, adverse effects, missed-dose management, and monitoring requirements) and self-reported practice behaviors. The intervention consisted of standardized face-to-face educational sessions supported by printed materials. Changes in knowledge and practice scores were analyzed using appropriate paired statistical tests. At baseline, most participants demonstrated poor warfarin-related knowledge despite high self- reported adherence. Following the educational intervention, there was a marked improvement across nearly all knowledge domains, with the mean knowledge score more than doubling and the majority of participants transitioning to a good knowledge category. Improvements were particularly notable in awareness of drug and food interactions, recognition of warning signs, and appropriate management of missed doses. Self-reported adherence remained high before and after the intervention, suggesting a ceiling effect. Overall, the study demonstrates that a brief, structured educational intervention is a feasible and effective approach to substantially improving warfarin-related knowledge in a low-resource outpatient setting, highlighting the importance of integrating patient education into routine anticoagulation care to enhance medication safety.