BACKGROUND: Immune checkpoint inhibitors (ICIs) are the gold standard therapy in patients with deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC). A significant proportion of patients show resistance, making the identification of determinants of response crucial. Growing evidence supports the role of sex in determining susceptibility to anticancer therapies, but data is lacking for patients with MSI-H CRC. METHODS: In this real-world cohort comprising 624 patients with MSI-H mCRC receiving ICIs, we investigated the impact of sex on patients' outcomes, overall and according to RESULTS: Although no differences were observed between females and males either overall or in the CONCLUSIONS: Overall, our findings suggest a complex interplay between sex and