Background <p>In recent years, new treatment options for chronic lymphocytic leukemia (CLL) have shown great potential. In China, the large CLL patient base translates into considerable clinical and economic burden, factors such as cost-effectiveness will be of significant importance in guiding government decision-making.</p> Objective <p>In this study, a cost-effectiveness analysis was conducted to assess the health economic value of two important first-line treatment options for CLL.</p> Methods <p>This study developed a partitioned survival model with three health states to analyze the cost-effectiveness (CE) of Venetoclax (Ven) + Obinutuzumab (Obi) and Chlorambucil (Chl) + Obi as first-line treatments for adult CLL. The transition probabilities were calculated using data from a clinical trial. Healthcare resource utilization and costs were obtained from publicly available data and expert interviews. The tool used to calculate quality-adjusted life years (QALYs) was derived from clinical trials and literature reviews. The primary outcome measure was the incremental cost-effectiveness ratio (ICER), expressed as cost per QALYs gained.We adopted a willingness-to-pay threshold of CNY 266,203 per QALY(China, 2022).</p> Results <p>In the base case, the Ven + Obi group obtained 1.29 QALYs more than the Chl + Obi group, with a cost reduction of 152,877.43¥. Sensitivity analysis and scenario analysis results showed that even when the main parameters in the model changed within plausible ranges, the ICER of the Ven + Obi group remained cost-effective. In probabilistic sensitivity analysis, 99% of the iterations were cost-effective under the threshold.</p> Conclusion <p>This study demonstrates that, the combination of Ven + Obi as a frontline treatment for CLL is superior to Chl + Obi in terms of cost-effectiveness. Sensitivity analysis indicates that treatment costs will significantly decrease after the patent protection period of these drugs expires.</p>