BACKGROUND: Irritable bowel syndrome (IBS) is a chronic functional disorder characterized by abdominal pain, bloating, and altered bowel habits. Post-infectious IBS (PI-IBS) develops after acute gastroenteritis, including infection (CDI). While CDI has been shown to decrease in prevalence during the pandemic era, studies indicate a substantial risk of PI-IBS following CDI, data remaining limited. The aim of the present study was to evaluate the risk of PI-IBS following a CDI and a potential correlation between PI-IBS onset and the severity of CDI. METHODS: This cross-sectional study included 69 patients hospitalized with suspected CDI at a tertiary center for Infectious Diseases, in Romania. Inclusion criteria were: patients >18 years of age with confirmed CDI via polymerase chain reaction. The severity of CDI was assessed based on hospitalization, laboratory parameters, and clinical symptoms. PI-IBS was evaluated six months after CDI using the Rome IV IBS questionnaire and the Bristol Stool Form Scale. Relative risk (RR) was calculated using SPSS software and a p value <0.05 was considered significant. RESULTS: Among the 38 enrolled patients, 24/38 (63%) were males, while 14/38 (37%) were females. The CDI was confirmed in 14/38 (37%) patients by PCR and the infection was ruled out in 24/38 (63%) patients (control group). PI-IBS developed in 57% of the CDI group compared to 25% in the control group (RR=2.29, 95% CI 0.99-5.23, 0.04). CDI severity correlated with higher PI-IBS risk, with 90% of hospitalized CDI patients developing PI-IBS (RR=2.72, 0.0493). CONCLUSION: PI-IBS occurred in over half of the patients six months after CDI, with disease severity increasing the PI-IBS risk. These findings highlight the need for proactive management in severe CDI cases to prevent long-term gastrointestinal complications.