Background: While warfarin and direct oral anticoagulants (DOACs) are used to manage thromboembolic events, they possess several features that impact adherence. Objective: To assess medication adherence and self-efficacy in patients receiving warfarin or DOAC treatment. Methods: A cross-sectional study was performed at Ibn Al-Bitar Hospital in Baghdad from December 2022 to May 2023 on patients receiving either warfarin or DOACs. The Arabic version of the Adherence to Refills and Medications Scale (ARMS) questionnaire and the Self-Efficacy for Managing Chronic Disease 6-Item Scale (SES6C) questionnaire were used to assess adherence and self-efficacy. Results: 181 patients were enrolled in the study, of whom 56.9% received warfarin and 43.1% received DOACs. The mean ARMS score was 13.71, and 81.77% of the patients were adherent to anticoagulant therapy. There was a significant difference in adherence between the warfarin and DOAC groups. The mean SES6C score for the participants was 50.01. Patients in the DOAC group had significantly higher self-efficacy compared to those in the warfarin group. The adherence score correlated significantly with patients’ gender, education level, hospitalization and duration of anticoagulant use, while the SES6C score did not correlate with any of the independent variables. There was a significant negative correlation between self-efficacy scores and medication adherence scores. Conclusions: Patients receiving DOACs showed a higher self-efficacy to manage chronic diseases and lower medication adherence as compared to warfarin. Higher self-efficacy was associated with higher adherence to treatment.