Background <p>Perihilar cholangiocarcinoma (CCA) is an aggressive malignancy that presents significant challenges in terms of diagnosis and treatment owing to its anatomical location. Liver resection and transplantation are the primary curative options; however, their long-term outcomes remain controversial. This study aimed to compare the long-term outcomes of protocol-based neoadjuvant selection and liver transplantation with liver resection for the management of perihilar cholangiocarcinoma.</p> Methods <p>A systematic review and meta-analysis were conducted according to the PRISMA guidelines. Electronic databases, including the Cochrane Library, PubMed/MEDLINE, and Embase, were searched for relevant clinical trials comparing liver transplantation with liver resection.</p> Results <p>Six studies comprising 768 patients (265 in the liver transplantation group and 503 in the liver resection group) were included. Liver transplantation was associated with significantly higher 5-year overall survival and 5-year disease-free survival. They also showed a higher 3-year disease-free survival rate. Patients in the liver transplantation group had a higher R0 resection rate. There were no significant differences in the 3- or 30-day postoperative mortality between the two groups.</p> Conclusion <p>Liver transplantation was associated with improved long-term survival in highly selected patients; however, these findings are limited by significant selection bias and the retrospective study design. The apparent long-term benefit observed with LT must be interpreted cautiously because transplant series frequently report post-transplant rather than intention-to-treat outcomes.</p>