Clostridioides difficile infections (CDI) are among the most common healthcare-associated infections worldwide, associated with significant morbidity and mortality rates. Even though several risk factors have been identified for (recurrent) CDI, including prior antibiotic use, it remains difficult to determine which patients are more likely to develop (recurrent) CDI and CDI-associated outcomes. In this project, all individuals with a recorded A04.7 code according to the ICD-10 classification between 2006 and 2019 were identified form the National Patient Registry and classified as CDI cases. Cases were matched by birthdate and sex with up to 10 controls derived from the Prescribed Drug Registry. Additional information on details of the exposure, outcome, or covariates was derived from the Cancer Registry, Causes of Death Registry and Registry for elderly and individuals with disabilities. This formed the basis for several large cohort studies where we investigated CDI-associated mortality and healthcare consumption. In the first cohort, individuals with CDI were compared to the full Swedish background population utilising Standardized Mortality Ratios (SMRs). Furthermore, they were compared to the matched controls by applying Incidence Rate Ratios (IRRs) which were additionally adjusted for age, sex, chronic comorbidities and drug use. The second cohort additionally compared all individuals with CDI to the controls by computing IRRs adjusted for age, sex, chronic comorbidities and drug use. In a third cohort study, all individuals with CDI were identified and classified into individuals with ongoing cancer, with a history of cancer or without recorded cancer to assess the risk of CDI recurrence associated with cancer. A case-control study was conducted to investigate the combined effect of recent (0-30 days pre-index date) and preceding (31-180 days pre-index date) antibiotic and proton pump inhibitor (PPI) use on the incidence and recurrence of CDI. From these studies, we can conclude that CDI remains an important infection that should not be ignored, even in younger populations without chronic comorbidities, since it is associated with considerable mortality and healthcare consumption rates. Our studies also show a complex relationship between CDI and cancer, where CDI may be a serious complication for individuals with cancer. Furthermore, our results suggest that PPIs and antibiotics are strongly associated with an increased risk of CDI, especially when combined and after recent exposure.