BACKGROUND: No published economic evidence currently exists with regards to idelalisib for relapsed chronic lymphocytic leukemia (CLL). Given its recent approval, comparator products on the market, and the high cost of care in this setting, there is a need for additional information on the clinical and economic impact of idelalisib to inform decisions about utilization, coverage, and reimbursement.  OBJECTIVES: The objective of this study was to evaluate the cost-effectiveness of idelalisib plus rituximab versus rituximab alone from a payer’s perspective. METHODS: We developed a partition survival model to evaluate idelalisib plus rituximab versus rituximab alone. The model included three health states – Pre-Progressed, Progressed, and Death. The pivotal trial Study 116 (Furman et al., 2014) served as the basis for this study by providing data on Progression-Free-Survival (PFS) and Overall-Survival (OS), dosing, and adverse events. We used longer-term data from a trial of bendamustine plus rituximab in CLL plus Weibull cumulative distribution functions to extrapolate incomplete PFS and OS curves. Cost data was derived from Wolters Kluwer Health, Centers for Medicare and Medicaid Services data, and publicly available literature. One-way and probabilistic sensitivity analyses were performed to evaluate uncertainty. We used a lifetime horizon, payer perspective, and a 3% discount rate. RESULTS: Total costs were $585,493 and QALYs were 3.34 for the idelalisib plus rituximab group, while total costs were $66,698 and QALYs were 1.20 for the rituximab alone group. This yielded an incremental cost-effectiveness ratio of $242,884/QALY. The result was most sensitive to changes in the hazard ratio for death and idelalisib drug costs. The probability that idelalisib was cost-effective was 1% at both a willingness to pay of $100,000/QALY and $150,000/QALY. CONCLUSIONS: Idelalisib plus rituximab does not appear to be cost-effective since it greatly exceeds the commonly cited thresholds of $100,000/QALY and $150,000/QALY. However, it is in line with other commonly used treatments in cancer.