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Aims: Hypertension is a serious health problem that requires lifelong treatment. The patient's nonadherence with antihypertensive medications is the major factor in treatment failure. Previous studies have suggested that adherence may be related to psychological factors consisting of personality traits. Materials and Methods: This cross-sectional study included 194 hypertensive patients referred to Alzahra Cardiovascular Clinic. The patients were asked to complete two questionnaires, including the NEO Big Five and adherence questionnaire. Results: Statistical analyses showed a significant negative correlation between neuroticism and medical adherence (CC = −0.148, PV = 0.002, CI = −0.240/−0.056), and extroversion had a significant positive correlation (CC = 0.161, PV = 0.001, CI = 0.260/0.052). The other aspects of personality traits had no significant correlation with medical adherence. Conclusion: Neuroticism may be a negative predictor and extroversion may be a positive predictor of medical adherence in hypertensive patients.