Background <p>Extreme temperature events (ETEs) are established mortality risks, yet evidence from tropical regions, especially on cold waves, remains limited. Most studies focus on urban heat, applying uniform national thresholds, which may overlook risks in climatically diverse regions. Using locally relevant ETEs definitions can better capture region-specific risks.</p> Objective <p>To investigate and compare the impacts of heat waves and cold waves on cardiovascular and respiratory mortality across 6 regions of Thailand, highlighting region-specific ETEs risks and vulnerable subpopulations.</p> Methods <p>Eighteen ETEs (HW1-HW9, CW1-CW9) were defined using station-specific temperature percentiles over 2–4 consecutive days. We conducted a two-stage time-series analysis of daily cardiovascular and respiratory mortality (2014–2022). Distributed lag non-linear models were fitted to data from 67 air monitoring stations, adjusting for air quality index, time trends, meteorological confounders, and COVID-19 lockdown effects. Region-specific relative risks (RRs) and 95% confidence intervals (CIs) were estimated over a lag of 0–21 days. A random-effects meta-analysis was used to pool region-specific risks. Vulnerable subgroup analyses were conducted by sex, age, and sub-diseases.</p> Results <p>Cold waves showed stronger and longer mortality effects than heat waves, with variation across definitions, regions, and subgroups. Cardiovascular mortality rose by 7.6% with cold waves (RR = 1.076; 95% CI: 1.061–1.090, lag 0–3), with a higher risk in females (8.9%) than males (7.0%). Heat waves elevated cardiovascular mortality by 2.4% among adults &lt;65. Regionally, the central region had the highest cold wave-related cardiovascular risk (CW9), while the northeast showed the strongest respiratory mortality with cold waves (CW9). Heat waves in the northeast and north increased cardiovascular (HW9, HW9) and respiratory (HW4, HW2) deaths, respectively. Nation pooled sub-disease analyses showed elevated cold-related risks for cerebrovascular deaths (RR = 1.108; 1.084–1.132) and chronic lower respiratory disease (RR = 1.059; 1.043–1.075).</p> Significance <p>Both heat and cold waves increased mortality in Thailand, with cold waves showing stronger and longer effects. These findings highlight the need for targeted adaptation strategies, including warning systems and insulation, especially in tropical settings.</p> Impact <p>This study added to the limited global evidence on extreme temperature-related mortality in tropical regions, especially cold waves, which emphasized a greater and more prolonged cardiovascular mortality risk than heat waves in Thailand. It was found to contrast with patterns seen in cold countries. Regional risks varied across the country’s diverse tropical climate zones. These findings highlighted the urgent need for public health interventions in tropical settings that address not only heat waves but also the underestimated burden of cold waves.</p>