Introduction We conducted a prospective, randomized, open-label, fixed-dose preference study, with a crossover design, using sildenafil, vardenafil, and tadalafil. Aim To assess patient preference for sildenafil (100 mg), vardenafil (20 mg), and tadalafil (20 mg) for the treatment of erectile dysfunction. Secondary objectives included finding out whether patients would follow treatment with a second or third option, in the event that the preferred drug was not available, and to assess side effects. Main Outcome Measures Patient preference for any treatment, and evaluation of the elements that patients would assess when choosing one of these drugs. Material and Methods Sildenafil (100 mg), vardenafil (20 mg), and tadalafil (20 mg) were taken at least six times over a period of 45–60 days with a washout period of 7 days. A total of 132 patients were enrolled to achieve a valid sample of 90 cases (15 per randomized group, total of six groups). Enrolled patients had mild to moderate erectile function. Results The International Index of Erectile Function (IIEF) score improved from baseline and was statistically significant in all cases (P < 0.0001). When we compared the IIEF scores, we found a statistically significant difference between tadalafil and vardenafil (P = 0.0002) favoring the former; similar results were obtained with the Erectile Dysfunction Inventory for Treatment Satisfaction (EDITS) Questionnaire (P = 0.000075). We also found a significant difference (P = 0.012) between tadalafil and sildenafil, again in favor of the former. In assessing drug preference, 25 patients (27.77%) chose sildenafil, 18 (20%) vardenafil, and 47 (52.22%) tadalafil. A total of 94% of patients would be willing to take another drug if the preferred choice was not available. All drugs were well tolerated. Conclusions Although this is a preference study based on subjective elements, statistically significant differences comparing the IIEF score and the EDITS Questionnaire lead us to believe that beyond patients’ subjective preference per se, said preference is probably also based on a genuinely superior response to one drug over another.

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