Objective: To evaluate the safety and effectiveness of daily 5-mg tadalafil treatment for men who have erectile dysfunction (ED) and premature ejaculation (PE), and to assess the long-term follow-up for ED and PE improvement persistence years after the cessation of medication. Patients and Methods: A prospective, single-blind, randomised study included 160 patients with ED and PE. All were evaluated using the International Index of Erectile Function (IIEF-5) questionnaire to evaluate ED and intravaginal ejaculatory latency time (IELT) for PE. Patients were subdivided into two equal groups. Group I (80 patients) treated with daily 5-mg tadalafil for 3 months, and Group II (80 patients) treated with a placebo for the same period. After 3 months of treatment and 2 years later after cessation of tadalafil, all patients were assessed for ED and PE. Results: The mean (SD) IELT and IIEF-5 score pre-treatment were 37 (11.24) s and 13.2 (4.2) for Group I, while in Group II they were 35.98 (10.8) s and 13.12 (4.11), respectively. After 3 months of treatment, the mean (SD) IELT in Group I showed a highly significant improvement from 37 (11.24) s to 120.5 (47.37) s (P < 0.001) but Group II showed no significant improvement from baseline to [39.43 (13.6) s; P > 0.05]. For the IIEF-5 score, there was a highly significant improvement from baseline to 20.45 (4.5) in Group I (P < 0.001), while there was no significant difference in Group II from baseline to [15 (4.84); P > 0.05]. At 2 years after cessation of tadalafil, there was statistically significant improvement in the IELT and IIEF-5 from baseline to endpoint . Conclusion: Oral daily 5-mg tadalafil was effective, tolerable, and safe treatment for patients with ED and PE. Long-term follow-up at 2 years confirmed the persistence of a significant improvement for both ED and PE.