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To study the association between ketorolac use and postoperative complications.Nonsteroidal anti-inflammatory drugs may impair wound healing and increase the risk of anastomotic leak in colon surgery. Studies to date have been limited by sample size, inability to identify confounding, and a focus limited to colon surgery.Ketorolac use, reinterventions, emergency department (ED) visits, and readmissions in adults (≥18 years) undergoing gastrointestinal (GI) operations was assessed in a nationwide cohort using the MarketScan Database (2008–2012).Among 398,752 patients (median age 52, 45% male), 55% underwent colorectal surgery, whereas 45% had noncolorectal GI surgery. Five percent of patients received ketorolac. Adjusting for demographic characteristics, comorbidities, surgery type/indication, and preoperative medications, patients receiving ketorolac had higher odds of reintervention (odds ratio [OR] 1.20, 95% confidence interval [CI] 1.08–1.32), ED visit (OR 1.44, 95% CI 1.37–1.51), and readmission within 30 days (OR 1.11, 95% CI 1.05–1.18) compared to those who did not receive ketorolac. Ketorolac use was associated with readmissions related to anastomotic complications (OR 1.20, 95% CI 1.06–1.36). Evaluating only admissions with ≤3 days duration to exclude cases where ketorolac might have been used for complication-related pain relief, the odds of complications associated with ketorolac were even greater.Use of intravenous ketorolac was associated with greater odds of reintervention, ED visit, and readmission in both colorectal and noncolorectal GI surgery. Given this confirmatory evaluation of other reports of a negative association and the large size of this cohort, clinicians should exercise caution when using ketorolac in patients undergoing GI surgery.