Recognition of antimicrobial resistance in equine practice has increased over the past decade. The objective of this study was to provide an updated retrospective review of antimicrobial regimens in one tertiary referral hospital and to evaluate the association with postoperative complications. A secondary objective was to evaluate other perioperative factors including surgical procedure, anesthetic and recovery parameters, and the effect of perioperative medications on complications and outcomes. A computerized search of medical records was performed to identify horses undergoing exploratory celiotomy from 1 January 2008 to 31 December 2021. A total of 742 celiotomies were performed (608 completed, 134 terminated intraoperatively). Factors recorded were evaluated using logistic regression for the presence of either incisional infection, postoperative ileus, or other complications postoperatively. Antimicrobial type or timing (pre-, intra-, or postoperative) were not associated with decreased risk of incisional infection or postoperative ileus; however, the duration of NSAID use was positively associated with incisional infection (OR 1.14 per day). Lidocaine and alpha-2-agonist administration postoperatively were also associated with increased incidence of postoperative ileus (OR 21.5 and 1.56, respectively). Poor recovery quality (OR 4.69), the addition of other antimicrobials besides penicillin/gentamicin postoperatively (OR 3.63), and an increased number of different NSAID classes used (OR 1.46 per additional) were associated with other complications. Implementation of enterotomy was associated with decreased risk of other complications (OR 0.64). These findings provide an updated summary of factors associated with postoperative complications in horses undergoing celiotomy.