OBJECTIVE: To update an earlier evaluation estimating the cost-effectiveness of quadrivalent influenza vaccination (QIV) compared with trivalent influenza vaccination (TIV) in the adult population currently recommended for influenza vaccination in the UK (all people aged ≥65 years and people aged 18-64 years with clinical risk conditions). METHODS: This analysis takes into account updated vaccine prices, reference costs, influenza strain circulation, and burden of illness data. A lifetime, multi-cohort, static Markov model was constructed with seven age groups. The model was run in 1-year cycles for a lifetime, i.e., until the youngest patients at entry reached the age of 100 years. The base-case analysis was from the perspective of the UK National Health Service, with a secondary analysis from the societal perspective. Costs and benefits were discounted at 3.5%. Herd effects were not included. Inputs were derived from systematic reviews, peer-reviewed articles, and government publications and databases. One-way and probabilistic sensitivity analyses were performed. RESULTS: In the base-case, QIV would be expected to avoid 1,413,392 influenza cases, 41,780 hospitalizations, and 19,906 deaths over the lifetime horizon, compared with TIV. The estimated incremental cost-effectiveness ratio (ICER) was £14,645 per quality-adjusted life-year (QALY) gained. From the societal perspective, the estimated ICER was £13,497/QALY. A strategy of vaccinating only people aged ≥65 years had an estimated ICER of £11,998/QALY. Sensitivity analysis indicated that only two parameters, seasonal variation in influenza B matching and influenza A circulation, had a substantial effect on the ICER. QIV would be likely to be cost-effective compared with TIV in 68% of simulations with a willingness-to-pay threshold of <£20,000/QALY and 87% with a willingness-to-pay threshold of <£30,000/QALY. CONCLUSIONS: In this updated analysis, QIV was estimated to be cost-effective compared with TIV in the U.K.