Objective: Infections in chronic lymphocytic leukemia (CLL) have been thoroughly investigated in the setting of clinical trials and single-center studies. However, large cohort studies on real-world data and studies on temporal trends are lacking. We performed a nationwide study on serious bacterial infections in CLL. Methods: Using high-quality Swedish government-based registries, 13 009 CLL patients diagnosed in 1982-2013 and their 49 380 matched controls were included. Results: Overall, CLL patients had an increased risk of serious inpatient bacterial infections with a hazard ratio (HR) 5.32 and 95% confidence interval (95% CI) 5.11-5.53, and the highest risk was observed for septicemia (HR 6.91, 95% CI 6.46-7.39) and lung infections (5.91, 5.64-6.18). The risk of serious inpatient bacterial infections decreased overtime with HR 0.87 (0.81-0.94) and HR 0.76 (0.70-0.82) in 1993-2002 and 2003-2013, respectively, compared to 1982-1992. CLL patients had an increased risk of death following a serious inpatient bacterial infection compared to matched CLL patients, and the risk was highest in the first 12 months after the infection (HR 5.48, 95% CI 5.11-5.90). Conclusion: We have, in this nationwide study, characterized the risk of serious bacterial infections in CLL patients and, importantly, depicted that the risk has decreased overtime. K E Y W O R D S chronic lymphocytic leukemia, immunology and infectious diseases, lymphoproliferative diseases S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Steingrímsson V, Gíslason GK, Aspelund T, et al. A population-based study on serious inpatient bacterial infections in patients with chronic lymphocytic leukemia and their impact on survival.