Introduction: Neurological disease is a known entity for causing erectile dysfunction (ED). Pharmacological therapies are not always effective these patients – penile prosthesis implant (PPI) is an established surgical treatment option. For a variety of reasons, neurological patients may experience differing outcomes of PPI compared to those whose ED arises from other causes. We investigated outcomes of PPI in neurological patients using the Italian multi-institutional national registry of penile prostheses [Italian Nationwide Systematic Inventarization of Surgical Treatment for ED (INSIST-ED)]. Methods: Patients undergoing PPI were investigated via the INSIST-ED registry, from 2014 to 2021. Data were prospectively recorded by 45 surgeons on a dedicated website ( www.registro.andrologiaitaliana.it ) and reviewed by a data manager. We subselected patients with neurological disease undergoing PPI for ED, and these patients were reviewed at 3, 6, and 12 months, and annually thereafter. Postoperative complications and functional outcomes were evaluated through validated questionnaires [International Index of Erectile Function-5 (IIEF-5), Sexual Encounter Profile 2–3, and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS)]. A nonvalidated questionnaire was administered to assess patient satisfaction. Results: A total of 33 patients were included with a median age of 49 [interquartile range (IQR) 41–55]. Median follow-up was 83 months (IQR 67–99.5). A penoscrotal approach for PPI was performed in most cases (90.9%), while infrapubic was used in three cases (9.1%). Inflatable and malleable devices were implanted in 30 (90.9%) and 3 cases (9.1%), respectively. Intraoperative complications occurred in one case (3%). Early postoperative complications (<90 days) were observed in three cases (9.1%): two wound dehiscence (Clavien-Dindo G1 and G3a respectively) and one device infection requiring prosthesis explant (Clavien-Dindo G3a). Mechanical failures of inflatable devices were not observed during the follow-up period. Median IIEF-5 before surgery was 8 (IQR 7–9). At the latest follow-up, IIEF-5 was 22 (IQR 19–23.5), and median EDITS was 79 (IQR 64–88). A total of 28 patients (84.8%) self-reported to be fully satisfied with the PPI. Conclusion: Although PPI in the neurological population has been historically considered to be at increased risk, in our study, PPI complications and infections rates in this cohort did not differ from general population.