Proton pump inhibitors are administered prophylactically in dogs treated surgically for acute thoracolumbar intervertebral disc extrusion (TL-IVDE). However, their efficacy in decreasing gastrointestinal (GI) complications is unknown. Omeprazole does not decrease the frequency of GI complications compared to placebo in dogs treated surgically for acute TL-IVDE. Thirty-seven client-owned dogs undergoing hemilaminectomy for acute TL-IVDE. Randomized double-blinded placebo-controlled prospective clinical trial. Dogs received PO placebo or omeprazole at 1mg/kg q12h for 5 days during hospitalization. Development of GI signs (e.g., diarrhea, vomiting, regurgitation, hematochezia, melena) was recorded daily. Clinicopathologic testing performed during hospitalization and at 2 and 4-week re-evaluations included: fecal occult blood, PCV, blood urea nitrogen/creatinine ratio, fecal calprotectin, canine pancreatic lipase immunoreactivity and fecal alpha-1 proteinase inhibitor concentrations. Omeprazole and placebo groups were compared using chi-squared or Fisher's exact tests. Gastrointestinal signs developed in 10/20 (50%) dogs in the omeprazole group and in 7/17 (41%) dogs in the placebo group (P= .59). Diarrhea was common (8/20 omeprazole, 5/17 placebo), hematochezia was rare (1/20 omeprazole, 1/17 placebo); melena was not observed. Clinicopathologic evidence suggestive of bleeding was present in 9/20 dogs treated with omeprazole and in 11/17 dogs that received placebo (P= .23). Fecal occult blood positivity was more common in dogs with GI signs (P= .03). Canine pancreatic lipase immunoreactivity was higher during hospitalization compared to re-evaluations (P= .01). Short-term, prophylactic omeprazole treatment did not decrease clinically detectable GI complications in dogs with acute TL-IVDE.