Background and Aims Perihilar cholangiocarcinoma (pCCA) is associated with poor prognosis. Radical resection remains the mainstay of treatment; however, high recurrence rates and limited overall survival (OS) after surgery. Metabolic syndrome (MetS) has been linked to unfavorable outcomes in various malignancies, but its impact on postoperative outcomes in pCCA is unclear. This study aimed to evaluate the influence of MetS on perioperative and long-term outcomes in patients undergoing radical resection for pCCA.Methods A retrospective analysis was conducted on 223 patients who underwent radical resection for pCCA at the First Affiliated Hospital of Army Medical University between January 2018 and December 2023. Patients were categorized into a MetS group (n=50) and a non-MetS group (n=173) according to diagnostic criteria. Perioperative complications, overall survival (OS), and recurrence-free survival (RFS) were compared between groups. Prognostic factors were identified using multivariate analysis.Results No significant differences were observed between the two groups regarding median hospital stay, overall complications, or severe complications (all P>0.05). The 1-, 3-, and 5-year OS rates in the MetS group were 62.3%, 22.3%, and 0, respectively, compared with 78.2%, 39.5%, and 22.0% in the non-MetS group. Corresponding RFS rates were 46.2%, 16.9%, and 0 in the MetS group vs. 63.8%, 29.6%, and 18.8% in the non-MetS group. Median OS and RFS were significantly shorter in the MetS group than in the non-MetS group (15.0 vs. 27.0 months; 12.0 vs. 21.0 months; P=0.021 and P=0.037, respectively). Multivariate analysis identified MetS and major vascular invasion as independent predictors of OS, while MetS, jaundice, R₀ resection, and major vascular invasion were independent predictors of RFS (all P<0.05).Conclusion MetS is significantly associated with worse long-term survival and higher recurrence risk after radical resection for pCCA. Incorporating MetS into preoperative assessment and postoperative management strategies may help improve patient outcomes.