Background: Historically, definitive surgical management with radical prostatectomy (RP) has only been considered an option for the treatment of localized prostate cancer (PCa). However, recent data may suggest a role for RP in advanced PCa treatment. Currently, there is limited data on the safety and perioperative outcomes of RP in this setting. Here, we aim to compare the perioperative outcomes of RP for locally advanced, node positive, and metastatic PCa using the American College of Surgeons National Surgical Quality Improvement Project (NSQIP) new procedure targeted database. Methods: RP procedures performed between 2019-2020 were identified. Patients were stratified to compare the effect of locally advanced disease (T3-4), node-positivity (N+), and metastasis (M+) against patients with localized (T1-2 N0 M0) PCa. Baseline demographics and 30-day outcomes, including operative time, hospital length-of-stay, 30-day mortality, readmissions, reoperations, major complications, minor complications, and surgery-specific complications, were compared between groups. Results: Pathologic staging data was available for 9,276 RPs. Baseline demographics were comparable. There was a slightly higher rate of minor-complications in the locally-advanced cohort, but no significant difference in major-complications, 30-day-mortality, readmissions, or rectal injuries. In comparison, while node-positivity was associated with longer operative time, LOS, and incidence of 30-day renal failure, it was not associated with a higher rate of any major, minor or surgery-specific complication. Similarly, RP for metastatic cases appeared to be comparably safe to those with M0 disease, although they were associated with a slightly higher rate of bleeding, prolonged-NG-tube use, and ureteral obstruction. Conclusions: RP for patients with locally advanced, node positive, and metastatic prostate cancer appears to be safe, and is not associated with significantly higher rates of 30-day mortality or major complications compared to localized prostate cancer. Given the previously demonstrated survival benefit in treating the primary tumor in advanced disease with radiation therapy, there may be a role for the RP in treating advanced PCa. Further studies are needed to better characterize the risks and benefits of surgery in these patients.