The purposeof this study is to investigate and compare the effects of 5-mg once-daily tadalafil versus 5-mg alternate-day tadalafil in men with moderate-to-severe erectile dysfunction (ED) and lower urinary tract symptoms (LUTS). Between January 2012 and June 2013, 144 men presenting with an International Index of Erectile Function-5 (IIEF-5) score of <18 and an International Prostate Symptom Score (IPSS) of >8 were enrolled to the study. Patients were allocated the simple alternate randomization into Group I (5-mg once-daily tadalafil) and Group II (5-mg alternate-day tadalafil). Changes in IIEF scores, Sexual Encounter Profile Question 3 (SEP Q3) percentage, IPSS, uroflowmetry and post void residual at the first visit (V1), week 4 (V2) and week 12 (V3) were compared. No significant difference was found between the baseline patient characteristics of Group I and Group II. Treatment with 5-mg daily tadalafil demonstrated improvement in IIEF, SEP Q3 percentage and IPSS score between V1 and V2, and that between V1 and V3. Patients receiving 5-mg alternate-day tadalafil also showed a significant improvement in IIEF, SEP Q3 percentage, and IPSS score between V1 and V2, and that between V2 and V3. However, no significant improvements were found in any other parameters. There were no significant differences between Group I and Group II apart from IIEF scores in V2 (19.4 versus 17.9, respectively). The SEP Q3 percentage was also higher at the V2 visit for Group I and Group II (35.6 versus 30.9%). Even with no placebo control and short of LUTS medication control, the use of 5-mg once-daily or alternate-day treatment with tadalafil was well tolerated in patients and effectively improved the IIEF score, IPSS score and SEP Q3 percentage. Management of patients with 5-mg alternate-day tadalafil could be adequate for regular use in patients with ED and LUTS.