Abstract Introduction Hydraulic penile prostheses have shown an overall good mechanical reliability up to 10 years after surgery; however, few data have been published on very long-term follow-up. Aim We looked at long-term (≥15 years) complications, including functional and quality of life (QoL) outcomes, after 3-piece inflatable penile prosthesis (IPP) implantation in patients with erectile dysfunction (ED). Methods Data regarding 149 patients submitting to IPP placement before 2001 were analyzed. All patients were implanted with AMS CX and Ultrex Plus 3-piece prostheses. Main Outcome Measure Patients were reassessed to evaluate rates of complications and functional outcomes. The validated questionnaire Quality of Life and Sexuality with Penile Prosthesis (QoLSPP) was used to assess patient QoL. Kaplan-Meier analysis estimated the probability of prosthesis survival (defined as working device/not-explanted). Results Median follow-up of 51 patients was 206 months (interquartile range [IQR], 145–257). The etiology of ED was vasculogenic (n = 20; 39%), Peyronie’s disease (n = 15; 29%), pelvic surgery (n = 4; 7.8%), organic other than vasculogenic (n = 3; 5.9%), or other (n = 9; 18%). Throughout the follow-up, 24 patients (49%) experienced complications: mechanical failure (n = 19; 79%), pain (n = 3; 12%), orgasmic dysfunctions (n = 1; 4.5%), or device infection (n = 1; 4.5%). The estimated IPP survival was 53% (95% CI, 36–67) at 20-year follow-up. Baseline characteristics (age, Charlson comorbidity index, body mass index, and erectile dysfunction etiology) were not significantly associated with the risk of IPP failure over time by Cox regression analysis. At 20-year follow-up, 41% (95% CI, 19–49) of the patients were still using the device. Among them, QoLSPP median domain scores were high: functional 22/25 (IQR, 20–23), relational 17/20 (IQR, 15–18), personal 14/15 (IQR, 12–15), and social 14/15 (IQR, 11–15). Clinical Implications The longevity of the device and long-term satisfaction rates should be comprehensively discussed during patient consultation for IPP surgery. Strengths & Limitations To our knowledge, this is the first study reporting long-term QoL outcomes using a dedicated questionnaire for penile prostheses. The low response rate for the telephone interviews, the retrospective design of the study, and the relatively small number of patients are the main limitations. Conclusion Long-term follow-up data after IPP placement showed that almost half of the devices still worked properly 20 years after the original penile implant, as 60% of patients were still using the device with high satisfaction and adequate QoL outcomes. Both patients and physicians should be aware of the expected life and outcomes of IPP implants.