INTRODUCTION: Naturalistic clinical trials provide data on the effectiveness of drugs in nonexperimental and everyday situations and are extremely helpful for decision-making purposes and for confirming experimental findings in clinical trials. No data have been published from naturalistic studies performed in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) with or without erectile dysfunction (ED) and treated with phosphodiesterase type 5 inhibitors. AIM: The aim of this study (TadaLutsEd Study) was to assess, in the context of medical practice, the effectiveness of tadalafil 5 mg once daily in patients with LUTS/BPH with or without erectile dysfunction. METHODS: The study was a 6-week uncontrolled, prospective, open-label, multicentric, observational study. The patient population involved sexually active males aged ≥ 50 years, diagnosed with LUTS/BPH with or without concomitant ED, and treated with tadalafil 5 mg daily in accordance with standard urological practice. MAIN OUTCOME MEASURES: Effectiveness was assessed through the self-administered International Prostate Symptom Score (IPSS) questionnaire; quality of life was evaluated through the IPSS quality of life section (IPSS-QoL). The patients were also evaluated with the International Index of Erectile Function (IIEF-5). Adverse events were recorded. Statistical analyses using paired data samples was applied (Wilcoxon signed-ranks test). RESULTS: Sixty-two patients (mean age 62.2 years) completed the treatment, of whom 85.5% showed improvement in their urinary symptoms. Pre- and post-treatment differences in the IPSS, IPSS-QoL, and IIEF-5 scores were statistically significant at 4.4, 1, and 5.4 points, respectively (P < 0.0001). Tadalafil was well tolerated, and adverse events were mild, with a discontinuation rate of 1.6%. CONCLUSION: According to study results, the use of tadalafil 5 mg once daily in a nonselected patient population with LUTS/BPH with or without ED led to improvements in terms of symptoms and quality of life and exhibited a safety profile similar to that obtained in controlled tadalafil clinical trials.