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We aimed to compare the efficacy of three tadalafil regimens for patients with type-2 diabetes mellitus (DM), at least one microvascular complication and erectile dysfunction (ED). Sixty patients attending our urology clinic with erectile problems and diagnosed with ED, having DM for at least 5 years, and at least one microvascular complication linked to DM were identified and randomly divided into three groups-Group I: used 5 mg tadalafil daily, Group II: used 20 mg tadalafil 2 h before sexual relations twice a week and Group III: used 5 mg tadalafil daily and an extra 15 mg tadalafil 2 h before sexual relations twice a week. After treatment, the median International Index of erectile function (IIEF-5) scores were significantly higher in Group III (15) compared to Groups I (8.5, p = 0.01) and II (9, p = 0.035). The groups were comparable in terms of the percentage of positive responses to the sexual encounter profile (SEP) 2 and the Global Assessment Questionnaires (GAQ)-1. However, the percentage of patients with positive responses to SEP-3 (20%, 40% and 75%, respectively) (p = 0.002) and GAQ-2 (20%, 45% and 75%, respectively) (p = 0.002) was significantly higher in Group III. Therefore, using a combination treatment (daily 5 mg + 15 mg when needed) to treat erectile function in patients with DM-related ED in the first stage may be more efficient with the same reliability and greater patient satisfaction.