Purpose Nausea and vomiting is the main cause of failure of enhanced recovery protocol (ERP) after right hemicolectomy. Methods From January 2013 to January 2018, all patients undergoing right hemicolectomy were prospectively included. Patients undergoing emergency surgery, additional complex procedure or temporary stoma, nasogastric tube (NGT) maintenance, or abdominal drainage were excluded. Failure of ERP was defined as nausea/vomiting precluding oral feeding after POD3 and/or the occurrence of postoperative ileus requiring NGT and/or length of stay (LOS) ≥ 8 days except for patients awaiting admission in rehabilitation unit. Risk factors of failure of ERP were identified using univariate and multivariate analysis.Results Among 306 patients undergoing right hemicolectomy, 140 fulfilled the inclusion criteria. Postoperative morbidity was 31%, and the mortality rate was nil. The mean postoperative hospital stay was 7 days (range 2–30). Successful ERP was achieved in 83 patients (59%). Causes of failure were major nausea/vomiting precluding oral feeding after POD3 in 36, postoperative ileus requiring NGT in 16 and LOS ≥ 8 days in 36. On multivariate analysis, preoperative anemia (OR 5.2; CI 95%, 1.3–21.1, p = 0.02) and platelet anti-aggregant/anti-coagulant (OR 4.5; CI 95%, 1.7–12.1, p = 0.003) were associated with the risk of failure of ERP. Conclusion This study shows that anemia and medication with antiplatelet/anticoagulation therapy increase the risk of failure of ERP after right hemicolectomy that translates most of the time by nausea/vomiting and postoperative ileus. The presence of these factors should lead to adapt the strategy to improve outcome rather than be considered as contraindication to ERP.