Introduction: Specific enhanced recovery after surgery (ERAS) guidelines for duodenopancreatectomy (Whipple) were published, mostly by extrapolating data from colorectal surgery. This study aimed to assess the feasibility of an ERAS protocol for duodenopancreatectomy by determining the compliance to the guidelines. Methods: Retrospective analysis based on a prospective database, including all consecutive patients undergoing duodenopancreatectomy within an ERAS program in four centers (Switzerland, United States, France, and Germany). Postoperative outcome (length of stay, complication according to Clavien classification) and compliance to the ERAS protocol (defined as the number of fulfilled element divided by the total number of recommended ERAS items) were analyzed. Results: Between October 2012 and June 2017, 404 consecutive patients with a mean age of 65 years (standard deviation +/− 12) underwent duodenopancreatectomy. Median length of stay was 14 days (interquartile range 9–22). There were 46 readmissions (11.8%). The 30 days overall complication rate was 83.3% (n = 325) with 46.2 % (n = 180) minor (Clavien grade I-II) and 37.2 % major (Clavien grade III-IV) complications. The 30 days mortality was 3.1% (n = 12). The pancreatic fistula rate was 30.5% (n = 119) and the delayed gastric emptying rate was 33.3% (n = 130). Mean overall compliance was 63.6% (Standard deviation (SD) +/− 9.5), with pre-, intra- and post-operative compliance of 92.9% (SD +/− 10.1), 80.8% (SD +/− 18.9), and 40.7% (SD +/− 15.3) respectively. Conclusion: Enhanced recovery after surgery protocol according to published ERAS guidelines can safely be performed with favorable outcome. A high compliance to the protocol was observed in the preoperative and intraoperative period.