The current study aimed to assess the performance of the 3-level complexity classification that stratified liver resection procedures into 3 complexity grades (grade I, low; grade II, intermediate; and grade III, high complexity) and to evaluate whether the Enhanced Recovery after Surgery (ERAS) protocol improves postoperative outcomes for each complexity grade. Consecutive patients undergoing open liver resection and laparoscopic liver resection at Lausanne University Hospital during 2010 to 2020 were assessed. A total of 437 patients were included. Operative time, estimated blood loss, and length of hospital stay increased significantly, with a stepwise increase of the grades from I to III in open liver resection and laparoscopic liver resection (all, p < 0.05). The same trend for Comprehensive Complication Index was found in open liver resection (p < 0.005). Age (p = 0.004), 3-level complexity classification (grade II vs I; p = 0.001; grade III vs I; p < 0.001), no use of the ERAS protocol (p = 0.016), and biliary reconstruction (p < 0.001) were significant predictors for postoperative complication, defined as Comprehensive Complication Index ≥ 26.2 in a multivariable logistic regression analysis. The prediction model incorporating the 4 factors had a calculated Concordance Index of 0.735 and 0.742 based on the bootstrapping method. The use of ERAS protocol was associated with lower probability of postoperative complication for each complexity grade and age. The use of ERAS protocol can decrease the probability of postoperative complication for each surgical complexity of liver resection and patient age. This finding emphasized the importance of tailoring perioperative management according to surgical complexity and patient age to improve outcomes after liver resection. Display omitted