Abstract: This retrospective cohort study explores the use of Bruton tyrosine kinase inhibitors (BTKi) in veterans with chronic lymphocytic leukaemia (CLL) and severe renal impairment (eGFR <30 mL/min/1.73 m²). The analysis included 115 predominantly male veterans, with a median age of 74 years, treated between January 2013 and December 2022. Over a median follow-up of 26 months, 34% experienced progression to severe renal dysfunction, with many cases having unknown causes. The study primarily involved ibrutinib (n=103), along with acalabrutinib (n=18) and zanubrutinib (n=3). Despite a 37% rate of dose reductions due to toxicity, the overall hematological response rate for ibrutinib was 81.5%. The median overall survival was 49 months, significantly lower than those with better renal function (eGFR ≥30 mL/min/1.73 m²). Notably, concurrent hemodialysis did not increase cardiovascular or infectious complications. The findings indicate that BTKi could be an effective treatment for CLL patients with severe renal dysfunction but highlight the need for careful monitoring and potential dose adjustments to manage toxicity. Further research is needed to assess long-term safety and outcomes in this population.