Studies have demonstrated a positive correlation between high body mass index (BMI) and an increased risk of infection (CDI), independent of antibiotic usage or healthcare exposures. To compare the outcomes of obese (BMI ≥ 30 kg/m) and non-obese (BMI < 30 kg/m) hospitalized patients with CDI. This retrospective cohort study included patients with CDI hospitalized in Beilinson hospital between January 2013 and January 2020. The primary outcome was 90-day all-cause mortality. Secondary outcomes included 30-day mortality, colectomy, intensive care unit (ICU) admission and length of hospital stay (LOS). Multivariate analysis was performed to identify the risk factors independently associated with 90-day mortality. The study included 889 patients: 131 (15%) obese and 758 (85%) non-obese. The obese group was younger (median age 65 years vs. 73 years ( < 0.01)) and with a higher rate of diabetes mellitus (57/131 (44%) vs. 180/758 (24%) ( < 0.01)). The 90-day mortality was lower in the obese group: 19/131 (15%) vs. 170/752 (23%) ( = 0.04). The 30-day mortality was 8/131 (6%) vs. 96/757 (13%) ( = 0.03). ICU admission was 9/131 (7%) vs. 23/758 (3%) ( = 0.03), and median LOS was 19 vs. 12 days ( < 0.01) in obese and non-obese groups, respectively. In the multivariable analysis, after adjustment for age, Charlson's comorbidity index ≥3, assistance in activities of daily living, treatment with proton pump inhibitors and severity of illness, obesity was not a significant risk factor for 90-day mortality (OR = 0.65, 95% CI: 0.38-1.01; = 0.1). In this study, obesity was not significantly associated with 90-day mortality after adjustment for other risk factors; however, ICU admission was higher and LOS longer in this group.