Abstract Introduction Penile prosthesis (PP) is the established treatment for patients with erectile dysfunction (ED) who do not respond to phosphodiesterase inhibitors and intracavernosal injections. In general, these devices have been largely successful but there are not free of serious complication such as PP infection (PPI). PPI requires immediate surgical removal or salvage rescue of the PP. Aim In this report, we present two clinical cases with inflatable PP (IPP) treated locally with antibiotic and high pressure irrigation and then avoid the PP removal or salvage rescue. Methods We present two patients with PPI in our institution and literature review. Main Outcome Measures Resolution of the two cases. Results Patient A (A) was 44 years old and patient B (B) 51 years old presented PPI after three weeks (A) and eight weeks (B). Both patients were diabetic. Physical exploration revealed an open scrotal incision at its margin with a clear discharge. The rest of the incision and scrotum were clean and dry. They had not scrotum pain/tenderness or systemic/septic symptoms. The bacterial culture of the incisional drainage revealed a Staphylococcus aureus (A) and Staphylococcus epidermidis (B). In both cases, we performed an excision of the tissue around the pump with a high pressure pulsed irrigation (Interpulse; Stryker Corp, Kalamazoo, MI, USA). For the irrigation we used three different solutions that included povidone-iodine, antibiotics (gentamicin plus vancomicin), and hydrogen peroxyde. Finally, we performed a multilayered surgical closure with the use of aspirate drainage over 24 hours and intravenous antibiotics. The patients had a total resolution of its symptoms after 20 months (A) and 36 months (B), and the IPP worked properly. Conclusion This treatment could be an option for to perform specific patients with local IPP infection without systemic symptoms instead of surgical removal.