Background: Historically, surgical management with radical prostatectomy (RP) has been a definitive treatment option only for localized prostate cancer (PCa). However, recent studies suggest an overall survival benefit to treating the primary tumor with radiation therapy in metastatic PCa (mPCa). Therefore, RP may have a role in treating mPCa, but the perioperative safety of that remains unclear. Here, we aim to compare the perioperative outcomes of RP for locally advanced, node positive, and metastatic PCa using the National Surgical Quality Improvement Project (NSQIP) database. Methods: RPs performed between 2019-2020 were identified in NSQIP and the corresponding Prostatectomy-Targeted Participant Use File. Cases were grouped into six distinct categories: T1N0M0-T2N0M0; T3N0M0; T4N0M0; T1-3N1M0; T4N1M0; and T1-4N0-1M1. Baseline age, race, and medical comorbidities were compared between the groups. Patients were then further grouped into T1-2N0M0 versus T3-4N0M0 cases to compare the effect of locally advanced disease, TanyN1M0 versus TanyN0M0 to compare the effect of node-positivity, and TanyN0M1 versus TanyN0M0 to compare the effect of metastases. 30-day outcomes, 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 was available for 5,248 RPs. Baseline demographics were largely similar, with the exceptions of increased Black race, diabetes, and smoking in the node-positive-group and increased age in the T4 group. There was a slightly higher rate of minor complications in the locally advanced (T3-4N0M0) versus localized (T1-2N0M0) group, but no significant difference in major complications, 30-day mortality, readmissions, or rectal injuries. In comparison to node-negative patients (T1-4N0M0), node-positivity (T1-4N1M0) was associated with longer operative time, LOS, and incidence of 30-day renal failure, but was otherwise not associated with a higher rate of any complication. Compared to non-metastatic cases (T1-4N0M0), metastatic cases (T1-4N0M1) were associated with a higher rate of bleeding, prolonged-NG-tube use, ureteral obstruction, and LOS. Conclusions: RP for patients with locally advanced, node positive, and metastatic prostate cancer appears to be safe; it is not associated with significantly higher rates of 30-day mortality or major complications compared to RP for localized prostate cancer. Given the potential survival benefit in treating the primary tumor in advanced disease, there may be a role for RP in treating patients with advanced PCa.