Background This study aimed to compare clinical outcomes of the middle hepatic vein (MHV)‐oriented versus conventional hemihepatectomy for perihilar cholangiocarcinoma (PHC). Methods From 2008 to 2017, medical records of patients undergoing hemihepatectomy with caudate lobectomy for advanced PHC were reviewed retrospectively. MHV‐oriented hepatectomy was defined as full exposure of the MHV on the dissection plane. Predictors of morbidity and survival were identified. Results A total of 125 patients were enrolled. MHV‐oriented and conventional hepatectomies were performed in 44 and 81 patients, respectively. The curative resection rate, blood loss, transfusion, and survival were comparable between two groups; however, severe morbidity rate was significantly lower in the MHV‐oriented group (9.1% vs 38.3%, P < 0.001). MHV‐oriented approach was an independent predictor of severe morbidity, as were the age, bilirubin level, and blood transfusion. Severe morbidity was associated with significantly decreased overall survival and recurrence‐free survival (RFS) (median 29.0 vs 46.9 months, P = 0.011 and 20.3 vs 31.1 months, P = 0.003, respectively). Multivariate analysis revealed that severe morbidity independently predicted shorter RFS (P = 0.025). Conclusions MHV‐oriented approach for advanced PHC is safe and associated with a significant decrease in severe morbidity. Severe morbidity adversely affects survival after surgery; therefore, optimal preoperative preparation and MHV‐oriented hepatectomy with meticulous dissection remain of critical importance.