Four horses were evaluated for clinical signs consistent with small intestinal disease. During exploratory surgery, primary hematomas in the mesentery were found in 2 horses. The third horse developed a hematoma secondary to a mesenteric rent, whereas in the fourth horse, a hematoma developed secondary to strangulation of the bowel by a mesenteric lipoma. Two horses were euthanatized at surgery, because the extensive nature of the hematoma precluded ligation and there was substantial risk of continued hemorrhage postoperatively. The remaining horses recovered from surgery but developed complications. One horse developed functional ileus and required a second surgery to decompress the bowel, whereas the second horse eventually was euthanatized for severe, recurrent signs of colic. Clinical signs and management of small intestinal lesions related to volvulus, epiploic entrapment, intramural hematoma, mesenteric rent, and intussuception have been described. To our knowledge, reports of small intestinal infarctions secondary to hematomas in the mesentery have not been published. Primary hematomas in the mesentery should be included in the differential diagnoses for horses examined for signs of depression, anorexia, and progressive signs of colic.