Background <p>National health insurance coverage for third-generation heat and moisture exchanger (HME) was approved in Japan for patients after total laryngectomy (TL). Our study evaluated the cost-effectiveness of third-generation HMEs (Provox^® Life™ such as Provox^® Life Night, Go, Home, Energy, and Protect) versus second-generation HMEs and no HME for patients who underwent TL in Japan.</p> Methods <p>A Markov model with five health states was developed using an existing model from a Japanese public healthcare payer perspective, with a time horizon of 10 years and a cycle length of one year. Primary outcome was incremental cost-effectiveness ratio (ICERs), while secondary outcomes were pulmonary infection, mucus plug event and skin irritation. One-way sensitivity analyses (OWSA) and Probabilistic Sensitivity Analysis (PSA) were also conducted to determine the robustness of model conclusions.</p> Results <p>Third-generation HMEs resulted in an ICER of JPY 2,350,010 per QALY gained, at a willingness-to-pay threshold of JPY 5,000,000 per QALY gained, as compared to second-generation HMEs, indicating cost-effectiveness. Similarly, with an ICER of JPY 4,708,917 per QALY gained, third-generation HMEs were also more cost-effective than no HME. Third-generation HMEs showed a decrease in pulmonary infections (average amounts of pulmonary infections per patient over 10 years: 0.26 vs. 0.39 and 0.55), mucus plug event (0.29 vs. 0.47 and 2.14) and skin irritation (1.80 vs. 2.78 and 0.00) compared to second-generation HMEs and no HME. According to OWSA, the transition probabilities between health states were the main drivers for the cost difference between third-generation and second-generation HMEs. PSA confirmed the robustness of the findings.</p> Conclusion <p>This is the first study to evaluate cost-effectiveness of HMEs in Japan, suggesting that third-generation HMEs (Provox^® Life™) are more cost-effective compared to second-generation HMEs and no HME for patients who underwent TL in Japan.</p>