OBJECTIVE In investigating possible immunologic causes of miscarriage, we hypothesized a more frequent maternal immune response in placental tissue in women miscarrying their first pregnancy, compared to woman miscarrying following at least one full-term delivery. METHODS We reviewed the medical charts of 273 consecutive women who had treatment for miscarriage. After application of the exclusion criteria, 32 patients were selected who had a full-term pregnancy outcome following the index miscarriage. The patients were divided into two groups based on the pregnancy order of the index miscarriage. Group 1 (n = 16) included women who lost their first pregnancy. Group 2 (n = 16) included women who miscarried a pregnancy after at least one full-term delivery. Miscarriage tissue was evaluated for placental and decidual histologic features of uteroplacental vasculopathy and chronic inflammation. RESULTS Lesions of chronic inflammatory and uteroplacental vasculopathy were generally more common in Group 1 as compared to Group 2, and the presence of more than one of the histopathologic lesions was significantly more frequent in Group 1 (37.5%, 6/16) than in Group 2 (0/16, P = .02, Fisher's Exact). CONCLUSIONS This study demonstrates more frequent lesions of chronic inflammation and uteroplacental vasculopathy in miscarriage patients with a first pregnancy loss, compared to those patients who have had a pregnancy loss following at least one full-term delivery.