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To evaluate the risk factors, incidence, and morbidity associated with the diagnosis of obstetric Clostridium difficile infection.We performed a retrospective cohort study on women admitted for delivery using the Healthcare Cost and Utilization Project Nationwide Inpatient Sample from the United States. The delivery admission records of pregnant women were reviewed between 1999 and 2013. After adjusting for demographic and clinical characteristics, we assessed risk factors for the diagnosis of C difficile infection using unconditional logistic regression.Of the total 13,881,592 births in our cohort, we identified 2,757 (0.02%) admissions for delivery complicated by a diagnosis of C difficile infection. During the study period, the rate of C difficile infection diagnoses among women hospitalized for delivery doubled from 15 (95% CI 11.87–16.96) to 30 (24.42–31.78) per 100,000 deliveries per year (P<.001). Risk factors associated with the diagnosis of C difficile infection included age older than 35 years, multiple gestations, smoking, Crohn's disease, ulcerative colitis, long-term antibiotic use, pneumonia, pyelonephritis as well as cesarean or perineal wound infection. The diagnosis of C difficile infection in pregnancy was associated with a significant increase in maternal death (8.0/1,000 vs 0.1/1,000, adjusted odds ratio [OR] 56.8, 95% CI 35.8–90.1). Furthermore, there was an increase in sepsis (46.4/1,000 vs 0.6/1,000, adjusted OR 59.1, 95% CI 48.8–71.6), paralytic ileus (58.0/1,000 vs 1.5/1,000, adjusted OR 33.1, 95% CI 27.5–39.8), venous thromboembolism (38.4/1,000 vs 3.1/1,000, adjusted OR 8.1, 95% CI 6.5–10.2), and hospital stays greater than 2 weeks (173.0/1,000 vs 6.5,1,000, adjusted OR 24.3, 95% CI 21.6–27.4) among pregnant women with C difficile infection.The diagnosis of C difficile infections in pregnancy has increased over the past 15 years and this diagnosis is associated with significant maternal morbidity and mortality.