Tadalafil 5 mg represents the standard for men with Erectile dysfunction (ED) and lower urinary tract symptoms (LUTS)/benign prostatic enlargement (BPE). We carried out an observational trial aiming to assess the efficacy and safety of Tadalafil compared with Tadalafil plus Tamsulosin. Seventy-five patients complaining of ED and LUTS were treated for 12-weeks with Tadalafil plus placebo (TAD+PLA-group) or with combination therapy tadalafil plus tamsulosin (TAD+TAM-group). Efficacy variables were: International Index of Erectile Function (IIEF), International Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax) and safety assessments. Data were evaluated using paired samples T-test (baseline vs. 12-weeks) and analysis of variance (Δgroup-TAD+PLA vs. Δgroup-TAD+TAM). At baseline, both groups presented similar characteristics and symptoms scores (all: p > 0.05). From baseline to 12-weeks, all the subjects showed a significant improvement of IIEF, total-IPSS, storage-IPSS, Qmax (all: p < 0.001). Conversely, a significant improvement of voiding-IPSS was observed in TAD+TAM-group (-3.5 points, p < 0.001). Indeed, TAD+PLA-group showed a not significant improvement of voiding-IPSS (-2.0 points, p = 0.074). When we compared between-groups differences at 12-weeks, IIEF (p = 0.255), total-IPSS (p = 0.084) and storage-IPSS (p = 0.08) did not show any statistically significant differences, whereas, voiding-IPSS and Qmax were significantly better in TAD+TAM-group (p = 0.006 and p = 0.027, respectively). No severe treatment adverse events (TAEs) were reported in both groups. Tadalafil achieved the same improvements of IIEF, total-IPSS, storage-IPSS when compared to combination therapy. Instead, Qmax and voiding-IPSS were better managed with combination therapy, without change of TAEs.