Erectile dysfunction (ED) is the most frequently reported male sexual dysfunction. Penile prosthesis implantation (PPI) is an effective solution for patients with medically refractory ED. Despite advancements in surgical techniques and device technology, detailed evidence on PPI complication rates is limited. A systematic review was conducted following PRISMA guidelines, including literature from Medline, Embase, Cochrane Libraries, and clinicaltrial.gov from 2000 to October 2024. Eligible studies included randomized controlled trials (RCTs), non-randomized comparative studies, and case series with ≥5 participants. Adult male patients (≥18 years) undergoing PPI for ED, Peyronie’s disease, or priapism were considered. Eligible interventions included malleable and hydraulic (two- or three-piece) prosthesis implantation, device explantation and reimplantation, and PPI combined with penile curvature correction. Primary outcomes were intraoperative and postoperative complication rates. Of the 1370 studies initially identified, 151 met inclusion criteria, encompassing a total of 92,777 patients. Device infections were reported in 103 studies, with rates ranging from 0.03–14.3%, predominantly under 5%. Erosion rates spanned 0.02–32.5%, with most studies reporting rates below 5%. Mechanical failure rates were highly variable, exceeding 15% in about half the studies with follow-up periods of 5 to 11 years. Intraoperative complications such as urethral injury and corporeal perforation were uncommon but occurred more frequently in patients with severe fibrosis, including those with priapism. Neurological comorbidities were associated with an elevated risk of mechanical failure, while diabetic patients did not exhibit a significantly increased infection risk compared to the general population. Modern techniques and coated devices have reduced infection and erosion rates. However, mechanical failure remains a concern, emphasizing the need for technological advancements. Tailored device selection and comprehensive pre- and postoperative management are critical to reducing revision rates and improving outcomes. Future research should address gaps in surgical approach optimization and complication management.