Background: Alvimopan is a novel peripheral mu receptor antagonist that is indicated for preventing post-operative ileus in patients undergoing abdominal surgery or bowel resection. Alvimopan has specific administration requirements when given to patients to prevent post-operative ileus. Methods: A retrospective cohort of 80 patients was identified by a primary procedure of colon/rectal surgery. The primary outcome assessed was rate post-operative ileus. To control for acuity difference, the random sample of 80 patients were stratified by Charlson score using Optum One software. The patients were randomly selected reviewing patients who received or did not receive alvimopan. Results: The rate of post-operative ileus with alvimopan 33.3% compared to 32.5% without alvimopan was comparable (p=0.45). The 30-day readmission rate for patients receiving and not receiving alvimopan were 17.7% versus 18.5%, respectively (p=0.077). The evaluation of the random sample of 80 patients failed to demonstrate a difference post-operative length of stay (p=0.26) in time to tolerate a diet (p=0.76) and use of antiemetics (p=0.35). There was a significant difference in the use of laxatives (p=0.008) and time to first bowl movement by 1.2 days (p=0.033) outcomes were similar with regards to post-operative ileus (p=0.459) and 30-day readmission (p=0.0775) with each measure failing to achieve significance. Conclusion: The similar outcome profile between postoperative ileus and 30-day readmission rate do not support the use of alvimopan. Other alternatives to prevent post-operative ileus should be considered, and further explore the clinical effectiveness with alvimopan with other studies with regards to dose, administration, and surgery types.