OBJECTIVES: Erectile dysfunction is a common male sexual disorder worldwide. Three oral medications – sildenafil, vardenafil, and tadalafil – have been used to treat erectile dysfunction. This study aimed to conjointly evaluate the therapeutic risks and benefits of the three medications to assist decision making of prescribing from the perspective of both physicians and patients. METHODS: A decision model was created to compare the risk-benefit of the aforementioned medications. Using published meta-analysis data, we performed a probabilistic Monte Carlo simulation to estimate the joint distribution of each type of adverse event (i.e., risk; categories included: any adverse event, serious cardiovascular (CV) events, headache, flushing, and dyspepsia) and effectiveness (defined as proportion of patients with improved erections). The incremental risk-benefit ratios (ICBRs) were calculated, and the results were illustrated by incremental risk–benefit planes. To account for differential risk preferences across patients, the results were also illustrated using risk–benefit acceptability curves and net-benefit curves. RESULTS: When risk was defined as having any adverse event, serious CV event, or headache, sildenafil was dominated by vardenafil (ICBR = -1.00, -0.20, and -3.20, respectively);  tadalafil showed increasing risk and benefit as compared to vardenafil (ICBR = 0.83, 0.03, and 0.13, respectively). Tadalafil dominated sildenafil and vardenafil when balancing between the risk of flushing/dyspepsia and the drug efficacy. CONCLUSIONS: Based on patients’ concern of various categories of adverse events and assuming negligible concern over medical costs, vardenafil or tadalafil may be preferred over sildenafil.