Inflatable penile prostheses (IPP) remain the gold standard for medically refractory erectile dysfunction (ED). Despite high overall success and satisfaction rates, infections remain a persistent and significant complication. In our clinical practice, we continued to experience high rates of infections despite use of a no-touch technique, voluminous irrigation, antibiotic-impregnated devices, post-op antibiotics, and multiple other intra-operative considerations. However, after switching from Betadine irrigation to Vancomycin / Gentamicin, we anecdotally noted an immediate reduction in infections, which prompted the current analysis. To compare the rate of IPP infections based on the type of intra-operative irrigation utilized: Betadine versus Vancomycin / Gentamicin. We reviewed a detailed, prospective database of men undergoing primary, revision, and salvage penile prostheses at our institution. The primary outcome was rate of penile prosthesis infection prior to and following change of intra-operative irrigation. It is notable that no other changes to operative or perioperative techniques occurred following the change in irrigation solution. Multiple variables were reviewed as potential confounders including patient demographics, comorbidities, type of surgery (primary, revision, salvage), number of prior prostheses, and adjunctive techniques. Univariate analysis was performed to evaluate for differences in rate of infection with use of Betadine versus Vancomycin / Gentamicin irrigation. Regression analysis was performed to control for variables noted to significantly impact infection rate.