Purpose: Many studies have shown that the enhanced recovery after surgery (ERAS) protocols improve postoperative surgical outcomes. The purpose of this study was to observe the effects on postoperative inflammatory markers and to explore the effects of a high degree of compliance and the use of epidural anesthesia on inflammation and surgical outcomes. Methods: Four hundred patients underwent colorectal cancer surgery at 2 hospitals during 2 different periods, namely, from January 2006 to December 2009 and from January 2017 to July 2017. Data related to the patient’s clinicopathological features, inflammatory markers, percentage of compliance with elements of the ERAS protocol, and use of epidural anesthesia were collected from a prospectively maintained database. Results: The complication rate and the length of hospital stay (LOS) were less in the ERAS group than in the conventional group (P = 0.005 and P ≤ 0.001, respectively). The postoperative white blood cell count and the duration required for leukocytes to normalize were reduced in patients following the ERAS protocol (P ≤ 0.001). Other inflammatory markers, such as lymphocyte count (P = 0.008), neutrophil/lymphocyte ratio (P = 0.032), and C-reactive protein level (P ≤ 0.001), were lower in the ERAS protocol group. High compliance ( ≥ 70%) was strongly associated with the complication rate and the LOS (P = 0.008 and P ≤ 0.001, respectively). Conclusion ERAS protocols decrease early postoperative inflammation and improves short-term postoperative recovery outcomes such as complication rate and the LOS. High compliance ( ≥ 70%) with the ERAS protocol elements accelerates the positive effects of ERAS on surgical outcomes; however, the effect on inflammation was very small.