Abstract Background We sought to decrease organ space infection (OSI) following appendectomy for perforated acute appendicitis (PAA) by minimizing variation in clinical management. Objective A postoperative treatment pathway was developed and four recommendations were implemented: 1) clear documentation of post-operative diagnosis, 2) patients with unknown perforation status to be treated as perforated pending definitive diagnosis, 3) antibiotic therapy to be continued post operatively for 4-7 days after SIRS resolution, and 4) judicious use of abdominal computed tomography (CT) scanning prior to post-operative day 5. Patient demographics and potential clinical predictors of OSI were captured. The primary end point was development of OSI within 30 days of discharge. Secondary endpoints included length of stay (LOS), readmission rate, other complications and secondary procedures performed. Results A total of 1246 appendectomies were performed and we excluded patients <18 years (n=205), interval appendectomies (n=51) or appendectomies for other diagnosis (n=37). Among the remaining 953 patients, 133 (14.0%) were perforated and 21 of these (15.8%) developed OSI. Comparing pre (n=91) to post (n=42) protocol patients, we saw similar rates of OSI (16.5 vs 14.3%, p=0.75) with a peak in OSI development immediately prior to protocol implementation which dropped to baseline levels 1 year later based on CUSUM analysis. Readmission rates fell by 49.7% (14.3 vs 7.1%, p=0.39) without increase in LOS (5.3 vs 5.7 days, p=0.55) comparing patients pre and post protocol, although these results did not reach clinical significance. Conclusions The implementation of and compliance with a post-operative protocol status post appendectomy for PAA demonstrated a trend towards diminishing readmission rates and decreased utilization of CT imaging, but did not affect OSI rates. Additional approaches to diminishing OSI following management of perforated appendicitis need to be evaluated.