OBJECTIVES: To assess the cost-effectiveness of ceritinib versus other therapies in the treatment of anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC) from the UK National Health Service (NHS) and Personal Social Service (PSS) perspective. METHODS: A partitioned survival model with three health states (progression-free, progressive, and death) was developed to compare ceritinib versus other treatments in patients with ALK+ NSCLC who were previously treated with chemotherapy (post-CT), or with an ALK inhibitor, regardless of prior chemotherapy (post-ALKi). The comparator arms included crizotinib, docetaxel, and pemetrexed in the post-CT population and best supportive care (BSC), docetaxel, and pemetrexed in the post-ALKi population. Progression-free survival and overall survival for ceritinib were estimated using  the ASCEND-1 (NCT01283516), ASCEND-2 (NCT01685060), and ASCEND-3 (NCT01685138) trial data. Parametric models were used to extrapolate outcomes beyond the trial period. Survival data for comparators were obtained from published clinical trials. Drug acquisition, administration, medical and adverse event (AE) costs were obtained from publicly available databases. Utilities for health states and disutilities for AEs based on EQ-5D were derived from literature. Incremental costs per quality-adjusted life year (QALY) gained were estimated comparing ceritinib vs. each comparator. Univariate and probabilistic sensitivity analyses were performed. RESULTS: Over 10 years, ceritinib was associated with 2.69 QALYs and total direct costs of ₤80,445 for post-CT population. The incremental cost per QALY was ₤30,536 comparing ceritinib vs. crizotinib, ₤44,847 vs. docetaxel, and ₤38,966 vs. pemetrexed. Among post-ALKi population, the QALY and total direct costs for ceritinib were 0.94 and ₤45,712 respectively. The incremental cost per QALY was ₤48,808 comparing ceritinib vs. BSC, ₤57,660 vs. docetaxel, and ₤40,145 vs. pemetrexed. Sensitivity analysis results were consistent with the base-case findings. CONCLUSIONS: Based on the willingness-to-pay threshold for end-of-life cancer drugs, ceritinib may be considered as a cost-effective option compared with other available therapies for previous treated ALK+ NSCLC.