Background: Acute mesenteric ischemia (AMI) is a challenging clinical problem associated with significant morbidity and mortality. Few contemporary reports focus specifically on patients undergoing open mesenteric bypass (OMB) or delineate outcome differences based on bypass configuration. This is notable, because there is a subset of patients who are poor candidates for endovascular intervention including those with flush mesenteric vessel occlusion, long segment occlusive disease, and a thrombosed mesenteric stent and/or bypass. This analysis reviewed our experience with OMB in the treatment of AMI and compared outcomes between patients undergoing either antegrade or retrograde bypass. Methods: A single-center, retrospective review was performed to identify all patients who underwent OMB for AMI from 2002 to 2016. A preoperative history of mesenteric revascularization, demographics, comorbidities, operative details, and outcomes were abstracted. The primary end point was in-hospital mortality. Secondary end points included complications, reintervention, and overall survival. Kaplan-Meier estimation and Cox proportional hazards regression were used to analyze all end points. Results: Eighty-two patients (female 54%; age 63 ± 12 years) underwent aortomesenteric bypass (aortoceliac/superior mesenteric, n = 44; aortomesenteric, n = 38) for AMI. A history of prior stent/bypass was present in 20% (n = 16). A majority (76%; n = 62) underwent antegrade bypass and the remainder received retrograde infrarenal aortoiliac inflow. Patients receiving antegrade OMB were more likely to be male (53% vs 25%; P =.02), have coronary artery disease (48% vs 25%; P =.06), chronic obstructive pulmonary disease (52% vs 25%; P =.03), and peripheral arterial disease (60% vs 35%; P =.05). Concurrent bowel resection was evenly distributed (antegrade, 45%; retrograde, 45%; P =.9) and 37% (n = 30) underwent subsequent resection during second look operations. The median duration of stay was 16 days (interquartile range, 9-35 days) and 78% (n = 64) experienced at least one major complication with no difference in rates between antegrade/retrograde configurations. In-hospital mortality was 37% (n = 30; multiple organ dysfunction, 22; bowel infarction, 4; hemorrhage/anemia, 2; arrhythmia, 1; stroke, 1; 30-day mortality, 26%). The median follow-up was 8 months (interquartile range, 1-26 months). The 1- and 3-year primary patency rates were both 82% ± 6% (95% confidence interval, 71%-95%), with 10 patients requiring reintervention. Estimated survival at 1 and 5 years was 57% ± 6% and 50% ± 6%, respectively. Bypass configuration was not associated with complication rates (P >.10), in-hospital mortality (log-rank, P =.3), or overall survival (log-rank, P =.9). However, a higher risk of reintervention was observed in patients undergoing retrograde bypass (hazard ratio, 3.0; 95% confidence interval, 0.9-11.0; P =.08). Conclusions: OMB for AMI results in significant morbidity and mortality, irrespective of bypass configuration. Antegrade OMB is associated with comparable outcomes as retrograde OMB. The bypass configuration choice should be predicated on patient presentation, anatomy, physiology, and surgeon preference; however, an antegrade configuration may provide a lower risk of reintervention.