Abstract Purpose Patients with cancer are vulnerable to Clostridioides difficile infection (CDI) due to their disease, treatment and regular hospital contact, yet if CDI-recurrence is more common remains unclear, and differences among cancer types remain unexplored. Methods This Swedish nationwide population-based cohort included all 43,150 individuals with recorded CDI (2006–2019) to assess CDI-recurrence in individuals with and without cancer, with binary multivariable logistic regression, stratified by anatomical location, and survival status. Results Compared to those without cancer (N = 29,543), ongoing cancer (diagnosis < 12 months; N = 3,882) was associated with reduced recurrence (OR = 0.81, 95% CI 0.73–0.89), while there was no association with cancer history (diagnosis ≥ 12 months; N = 9,725). There was an increased 8-week all-cause mortality (Ongoing cancer: OR = 1.58, 95% CI 1.43–1.74; Cancer history: OR = 1.45, 95% CI 1.36–1.55) compared to those without cancer. Among CDI-survivors, those with ongoing cancer presented with a decreased odds of recurrence (OR = 0.84, 95% CI 0.76–0.94), compared to those without cancer history, with no association for those with cancer history (OR = 1.04, 95% CI 0.97–1.1). Large variations were seen across cancer types, with the highest observed proportion of recurrence in oral and mesothelial cancer, and the lowest for esophageal cancer, although no statistically significant OR were found. Conclusion The population-based study indicates that individuals with cancer may have fewerrecurrences than expected, yet variations by cancer type were large, and mortality was high.