OBJECTIVES Treatment options for chronic lymphocytic leukemia (CLL) who received prior therapy are limited; no standard of care exists. In a recent phase III clinical trial (PCYC-1112), ibrutinib, an oral, once-a-day, first-in-class covalent Bruton’s tyrosine kinase inhibitor, was associated with improved progression-free survival (PFS, HR=0.215) and overall survival (OS, HR=0.387) compared with ofatumumab. The current study aimed to evaluate the projected life years (LYs) and quality-adjusted LYs (QALYs) associated with ibrutinib, ofatumumab, and other therapies for treatment of CLL with prior therapy. METHODS A health state model simulated treatment of a cohort of CLL patients who had received prior therapy. Patients were simulated to receive either ibrutinib or ofatumumab until death or disease progression, at which point they received subsequent treatment or best supportive care. Clinical inputs for ibrutinib and ofatumumab were informed by PCYC-1112 trial data (N=391). Long-term follow-up data from PCYC-1102 and PCYC-1103 trials (combined N=101) was used in sensitivity analysis. Long-term OS and PFS were extrapolated from clinical trials to estimate survival outcomes. Utility were informed by published studies. Evaluation of ibrutinib versus other existing agent and emerging agents including idelalisib and ABT-199 was included in a sensitivity analysis. Long-term health outcomes were discounted by 3.5%. RESULTS Treatment with ibrutinib resulted in better health outcomes, incrementally increasing LYs by 0.63 and progression-free LY by 0.87 over a 5-year time horizon compared to ofatumumab, which lead to 0.47 incremental QALYs. In a 10 year time horizon analysis, ibrutinib increased LYs by 0.79. Ibrutinib was also associated with increased LYs and QALYs compared to other existing and emerging treatments. The model results are most sensitive to the approaches used to extrapolate OS. CONCLUSIONS Ibrutinib was demonstrated to yield better health outcomes for CLL patients with prior therapy compared to ofatumumab, largely driven by significant improvements in PFS and OS.