Previous studies have suggested that vasodilator therapy may be beneficial for patients with nonocclusive mesenteric ischemia. However, robust evidence supporting this contention is lacking. We examined the hypothesis that vasodilator therapy may be effective in patients diagnosed with nonocclusive mesenteric ischemia. Retrospective cohort study. The Japanese Diagnosis Procedure Combination inpatient database. A total of 1,837 patients with nonocclusive mesenteric ischemia from July 2010 to March 2018. None. We compared patients who received vasodilator therapy (vasodilator group; n = 161) and those who did not (control group; n = 1,676) using one-to-four propensity score matching. Vasodilator therapy was defined as papaverine and/or prostaglandin E1 administered via venous and/or arterial routes within 2 days of admission. Only patients who did not receive abdominal surgery within 2 days of admission were analyzed. The main outcomes were in-hospital mortality and abdominal surgery performed greater than or equal to 3 days after admission. After propensity score matching, in-hospital mortality was significantly lower in the vasodilator group (risk difference, -11.6%; p = 0.005). The proportion of patients who received abdominal surgery at greater than or equal to 3 days after admission was also significantly lower in the vasodilator group (risk difference, -10.2%; p = 0.002). Vasodilator therapy with papaverine and/or prostaglandin E1 is associated with lower in-hospital mortality and prevalence of abdominal surgery in patients with nonocclusive mesenteric ischemia.