Background: The incidence of Clostridioides difficile infection (CDI) in peripartum women is rising, but limited data on its effect on maternal and neonatal outcomes are available., Objective: To study the effect of peripartum CDI on pregnancy and neonatal outcomes., Design: Retrospective cohort study., Methods: Patients with peripartum CDI 12 weeks before pregnancy through 6 weeks postpartum (January 1996-February 2018) were matched with controls (peripartum women without CDI) 1:1 by age, year of delivery, and prior pregnancies. McNemar's test and conditional logistic regression were used to analyze the effect of CDI on pregnancy and neonatal outcomes (complications, mode of delivery). p < 0.05 was considered statistically significant., Results: Overall, 101 cases and 100 controls (1997-2018) were included; median age 27 (range, 20-41) years. Timing of CDI was as follows: pre-pregnancy: 15.8% ( n = 16), during pregnancy: 51.5% ( n = 52), and postpartum: 32.7% ( n = 33). The commonest risk factor was outpatient/emergency room visits. Pregnancy and neonatal outcomes were analyzed for 67 matched pairs with CDI before or during pregnancy. Cases had higher odds of cesarean delivery ( p = 0.02) and lower odds of Group B Streptococcus (GBS) infection/colonization ( p = 0.03). Odds of cesarean delivery remained high after controlling for labor arrest disorders [odds ratio (OR): 17.23 (95% confidence interval (CI), 2.19-543.19; p = 0.004)]; odds of GBS remained low after controlling for antibiotic use (OR: 0.25, 95% CI, 0.04-0.99; p = 0.049). Neonatal outcomes were similar in cases and controls. CDI treatment did not affect treatment-related or delivery outcomes., Conclusion: Peripartum CDI was associated with higher odds of cesarean delivery and lower odds of GBS infections. Larger studies exploring the effect of CDI on pregnancy and neonatal outcomes are needed., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2023.)