Abstract Background Available evidence falls short in assessing the risk of all-cause mortality and cardiovascular disease (CVD) mortality among individuals with hypertension residing at various altitudes. This study’s objective was to investigate the correlation between residential altitude and the rates of all-cause mortality and CVD mortality among hypertensive patients. Methods This prospective cohort study encompassed 67,275 hypertensive individuals aged 35 years and above in the year 2018. Participants were categorized into four distinct groups based on their residence altitude: those living below 500 meters, between 500 and 1499 meters, 1500 to 2500 meters, and above 2500 meters. The study spanned a mean follow-up duration of 4.78 years. The associations between residential altitude and the risks of all-cause and CVD mortality were analyzed using Cox proportional hazards regression models. Results Among the 67,275 hypertensive patients included in the study (mean age of 63.9 years, with 45.3% being male), 8,768 deaths were recorded, of which 5,666 were attributed to CVD. Following multivariate adjustment, when compared to the group residing at altitudes below 500 meters, the groups living at altitudes of 500-1499 meters, 1500-2500 meters, and above 2500 meters exhibited significantly elevated risks of all-cause mortality [hazard ratio, HR = 1.45 (95% CI: 1.36-1.54), 1.35 (95% CI: 1.36), and 1.41 (95% CI: 1.28-1.54), respectively] and CVD mortality [HR = 1.47 (95% CI: 1.35-1.58), 1.42 (95% CI: 1.33-1.52), and 1.46 (95% CI: 1.31-1.62), respectively]. For each 500-meter increment in altitude, the risk of all-cause and CVD mortality increased by 10% and 11%, respectively. Subgroup analyses and sensitivity assessments consistently supported this association. Conclusions This study’s findings indicate a substantial connection between long-term residential high-altitude exposure and increased risks of all-cause mortality and CVD mortality among individuals with hypertension. Key messages • Increased altitude of residence increases the risk of subsequent all-cause and CVD mortality in hypertensive patients. • This study highlights that relevant guidelines and healthcare providers should consider altitude as an important factor in reducing the burden of hypertension and CVD.