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Background Low cardiorespiratory fitness, defined by reduced maximal oxygen consumption (VO2), is a predictor of mortality in patients without chronic disease. However, the relation between ventilatory efficiency (as measured by the slope of the relation between ventilation (VE) and carbon dioxide production (VCO2)) and all-cause mortality is unknown. Purpose To assess the relation between variables derived from cardiopulmonary exercise testing and long-term survival in normal subjects Method We recruited 145 healthy subjects, with no history of chronic disease (57% male, mean age 63±12) from primary care at random. All participants underwent cardiopulmonary exercise testing at baseline. Participants were followed for 15.5±3.5 years. The primary end-point was all-cause mortality. Cox-proportional hazard models were used to assess the relationship between measures of exercise performance and outcome. Hazard ratios (HR) are reported with 95% confidence intervals (CI). Results During follow up, 34 participants (23.4%) died. On univariable analysis, VE/VCO2 slope, peak VO2, respiratory exchange ratio at peak exercise, peak heart rate and 6-minute walk test distance were significant predictors of all-cause mortality (table 1). However, only VE/VCO2 slope (HR per unit increase: 1.13, 95% CI: 1.00–1.28, P=0.043) and peak heart rate (HR per 10 unit increase: 0.73, 95% CI: 0.57–0.93, P=0.010) were independent predictors of all-cause mortality on multivariable analysis. Table 1. Cox regression analysis (univariable and multivariable) for cardiopulmonary exercise testing measures and all-cause mortality HR Presentation Univariable analysis Multivariable analysis HR 95% CI p value HR 95% CI p value Peak VO2 (ml/kg/min) Per unit increase 0.90 0.86–0.95 Conclusions Raised VE/VCO2 slope is an independent predictor of all-cause mortality in healthy patients with no history of chronic disease.