OBJECTIVE: The objective was to compare perioperative factors that may influence clinician decisions regarding antimicrobial therapy duration and outcomes in horses undergoing exploratory celiotomy. ANIMALS: Horses > 1 mo of age undergoing exploratory celiotomy for colic that survived without repeat celiotomy for >/= 5 d. PROCEDURE: Retrospective cohort study. Cases were grouped by duration of antimicrobial therapy: G1, </= 24 h; G2, 1 to 3 d; G3, > 3 d. Admission, surgical, and postoperative data from the medical records and long-term outcome assessed via telephone follow-up were compared among groups. RESULTS: In total, 187 horses (67, 52, and 68 for G1, G2, and G3, respectively) were included. Differences in proportions of horses with strangulating lesions (29.9, 46.2, and 52.9%), undergoing enterotomy (23.9, 61.5, and 52.9%), and treated with resection/anastomosis (11.9, 28.9, and 39.7%) were identified (P = 0.02, P < 0.0001, and P = 0.001). Overall incisional infection rate in hospital was 12.8%, with no difference among groups (10.4, 13.5, and 14.7%; P = 0.80). Differences in proportions of horses with gastrointestinal (29.9, 42.3, and 55.9%; P = 0.009) and other inflammatory/infectious (13.4, 33.1, and 36.8%; P = 0.007) postoperative complications were identified. There was no difference among groups in survival to discharge (97.0, 96.2, and 89.7%; P = 0.20). Horses in G3 had increased duration of hospitalization [11 d (5 to 48 d)] versus G1 [8 d (5 to 63 d)] (P < 0.0001). Cost of hospitalization was higher for horses in G3 [$9410 ($3790 to $29 240)] than for those in G2 [$7340 ($1860 to $15 260)], which was higher than for those in G1 [$5330 ($3280 to $17 140)] (P < 0.0001). CONCLUSION: Antimicrobials were used for a longer duration in horses with more compromised bowel, after surgical procedures that entered intestine, and in cases with a variety of postoperative complications. Of note, incisional infection was a complication not associated with duration of therapy. Limited case numbers in some subgroups reduced statistical power, and findings should be interpreted accordingly. CLINICAL RELEVANCE: Operative and postoperative factors associated with longer duration of antimicrobial use in this study have been previously identified to influence clinical decision-making regarding the duration of antimicrobial therapy. However, the similar rate of incisional infection among groups suggests that this risk should minimally influence clinicians when deciding upon the duration of therapy. This study highlighted that further prospective, blinded studies are required to determine the risks and benefits of antimicrobial use in the postoperative period.