Background - Cardiac resynchronization therapy (CRT) in heart failure is plagued by too many nonresponders. The aim of the present study is to evaluate whether the estimation of myocardial performance by pressure-strain loops (PSLs) is useful for the selection of CRT candidates. Methods - Ninety-seven patients undergoing CRT were included in the study. Bidimensional and speckle-tracking echocardiography were performed before CRT and at the 6-month follow-up (FU). Conventional dyssynchrony parameters were evaluated. Left ventricular (LV) constructive work (CW) and wasted work (WW) were estimated by PSLs. Positive response to CRT (CRT+) was defined as ≥15% reduction in LV end-systolic volume at FU and was observed in 63 (65%) patients. Results - The addition of CW > 1,057 mm Hg% (area under the curve, 0.72, P < .0001) and WW > 384 mm Hg% (area under the curve, 0.67, P = .005) to a baseline model including clinical, echocardiographic, and conventional dyssynchrony parameters significantly increased the model power (χ, 25.11 vs 47.5, P < .0001). In this model, septal flash (odds ratio [OR] = 2.78; P = .001), CW > 1,057 mm Hg% (OR = 9.49; P = .002), and WW > 384 mm Hg% (OR = 16.24, P < .006) remained the only parameters associated with CRT+. The combination of CW > 1,057 mm Hg% and WW > 384 mm Hg% showed a good specificity (100%) and positive predictive value (100%) but a low sensitivity (22%), negative predictive value (41%), and accuracy (49%) for the identification of CRT+. Conclusions - The estimation of CW and WW by PSLs is a novel tool for the assessment of CRT patients. Although these parameters cannot be used by their own to select CRT candidates, they can provide further insights into the comprehension of dyssynchrony mechanisms and contribute to improving the identification of CRT responders.