BackgroundThere is limited research available concerning the risk anastomotic leakage in the context of Clostridium difficile infection (CDI). Herein, we aim to elucidate the correlation between CDI, encompassing both preoperative asymptomatic C. difficile carriers (CDC) and postoperative hospital acquired C. difficile infections (HA‐CDI), and the occurrence of anastomotic leakage in patients undergoing oncological colorectal surgery.MethodsThis is an observational, single‐center study. Data were sourced from surgical logs between 2018 and 2023, via the hospital's electronic system. Patients were split into three subgroups: CDC, HA‐CDI, and control group (CG). Groups were compared in terms of patient characteristics, morbidity, and mortality via Fisher's exact test and Kruskal–Wallis test. One‐to‐one propensity score matching was performed to reduce selection bias.ResultsA total of 522 patients were analyzed, split into three subgroups: CDC, n = 35; HA‐CDI, n = 27; CG, n = 460. One‐to‐one propensity score matching reduced the CG to 62 patients. Patients in the HA‐CDI group had higher rates of overall morbidity (p < 0.0001), higher rates of anastomotic leaks (p = 0.002), more surgical site infections (SSI) (p = 0.001), and a longer length of stay (26 vs. 11.2 vs. 9.3 days, p < 0.001), while patients in the CDC group had comparable rates of complications with the CG.ConclusionHA‐CDI is associated with a higher risk of anastomotic leak after oncological colorectal surgery, while asymptomatic CDC do not have higher morbidity and may be operated electively, under standard CD treatment.