Background: Cardiopulmonary exercise tests (CPET)assess oxygen uptake (VO2) and ventilatory efficiency (VE/VCO2 slope) as both are predictive measures of cardiovascular disease (CVD) severity in symptomatic adults. Specifically, the VE/VCO2 slope is a powerful prognostic tool for assessing CVD severity and prognosis as it is effectively independent of a patient’s capacity to reach volitional fatigue. In asymptomatic adults, several clinical risk factors for CVD have been established for use in health assessments, and as a method for early CVD detection and prevention. Therefore, we evaluated the relationship between the VE/VCO2 slope and several clinical CVD risk factors in at-risk but asymptomatic middle-aged obese adults. Methods: 29 obese adults (Mean ± SE; Age 46.5 ±2.6 years; BMI 35.9 ±1.1 kg/m2) were stratified into low (LR<2 risk factor) or moderate risk (MR≥2 risk factors) from self-reported health history questionnaires and quantitative assessments and performed a treadmill CPET. Results: No differences in VE/VCO2 slope between risk groups (LR30.1 ±1.8, MR29.2 ±0.9 VE/VCO2 slope). The VE/VCO2 slope positively associated with age and diastolic blood pressure (DBP) and not with the CVD risk factors BMI, HDL-C, LDL-C, fasting blood glucose, systolic blood pressure, or total risk factors; further DBP was the only predictor(r=0.429, r2=0.184, p= 0.037). Conclusion: DBP predicted a steeper ventilatory efficiency (VE/VCO2 slope) in at-risk but asymptomatic for CVD middle-aged obese adults. Our findings indicate that the ventilatory efficiency slopes CVD risk and prognosis assessment extends to clinically at-risk middleaged asymptomatic obese adults, and may function as an additional measure for long-term health monitoring.