Background: Patients with coronary artery diseases (CAD) use a wide spectrum of medications; hence, strategies are needed to increase their adherence. In this line, identifying factors associated with medication self-efficacy can be useful. Objectives: The current study aimed to investigate medication self-efficacy and its related factors in patients with CAD in the north-east of Iran. Methods: In this cross-sectional study, 104 patients with CAD hospitalized in one of the largest teaching hospitals in the north-east of Iran are studied. Participants were selected by convenience sampling method. Data were collected using Demographic and clinical information form, Information Satisfaction questionnaire (ISQ), and Self-Efficacy for Appropriate Medication Use scales (SEAMS). Data were analyzed by SPSS version 22 using descriptive statistics and multiple regression test. Results: The mean age of patients was 52.3 ± 8.8 years. The mean medication self-efficacy score was 24.9 ± 9.5 (out of 39). Multiple regression showed a linear and significant association between information satisfaction, income, medications used in the last month, information about the nature of the disease, doctors as a preferred source of information, nurses, family members, internet and social networks as the most information sources used by patients, with medication self-efficacy (R = 0.907, P < 0.001). These variables could explain 82.2% of the self-efficacy variance. Conclusions: Based on the result, it can be argued that in designing and implementing educational interventions aimed to promote medication self-efficacy in patients with CAD, individuals with lower income and under long-term medication treatment should receive more support. Educational programs should emphasize more on explaining the nature of the disease to the patients, and physicians should be more involved in educating patients.