Objective: This study sought to determine the contractile reserve (CR) response to exercise stress echocardiography (ESE) quantified by the novel parameter, non-invasive myocardial work (MW), in subjects with angiographically proven coronary artery disease (CAD). Methods: CR was measured by the relative change in ejection fraction (EF), global longitudinal strain (GLS) and MW indices from rest to peak exercise in 304 patients referred for clinically indicated ESE. Positive ESE patients proceeded to coronary angiography and further risk stratified based on either percutaneous or surgical intervention. Results: CRGLS and global work index (CRGWI) significantly decreased with exercise induced ischemia and angiographically proven significant CAD (CRGLS −1.6±3.5%; CRGWI −8.6±511 mm Hg% decrement, p < 0.001) compared to non-ischemic patients (CRGLS 1.4±2.2%; CRGWI 398±404 mm Hg% improvement). Global constructive work (CRGCW) was significantly higher (p < 0.0001) in non-ischemic (818±457 mm Hg%) and blunted in ischemic patients (208±550 mm Hg%). CRGCW (AUC.81; 95%CI:.75–.86) demonstrated the most association for inducible ischemia followed by CRGLS (AUC.75; 95%CI:.69–.80), CRGWI (AUC.73, 95%CI:.67–.79) and CREF (AUC.71; 95%CI:.65–.77, p < 0.001). Subgroup analysis showed patients requiring surgical revascularization demonstrated a significantly lower CRGWE (−11.5±7.6%, p < 0.05) as a result of reduced CRGCW (281±573 mm Hg%, p < 0.05) and increased global wasted work (CRGWW, 289±151 mm Hg%, p = 0.09). Conclusion: Multivessel disease requiring surgical revascularization have the greatest reduction in CR. MW may potentially improve detection of ischemia and further risk stratification during ESE to maximize the benefits of revascularization.