AIMS: Two-dimensional (2D)-strain derived from speckle-tracking is an alternative to tissue velocity imaging (TVI)-based strain. We compared their feasibility and accuracy in 150 patients undergoing dobutamine stress echocardiography (DSE) and coronary angiography. METHODS AND RESULTS: 2D- and TVI-strain were obtained in three apical views at rest and peak stress. Peak systolic strain rate (SR), endsystolic strain (epsilon(end-sys)), and peak strain (epsilon(peak)) were measured off-line at rest and peak stress, and results were compared with wall motion analysis and significant coronary artery disease (CAD > or = 70% diameter stenosis). Optimal cut-offs were derived from receiver operating characteristic (ROC) curves for sentinel segments. The most feasible method was 2D-strain at rest, and TVI-strain at peak stress. The average peak SR and epsilon(end-sys) at peak stress in segments of patients with significant CAD was less than in segments of patients without CAD (P < 0.0001) and mean PSI at peak stress was higher (P < 0.0001) with both 2D- and TVI-strain. Peak systolic SR at peak stress had the best area under the ROC for both 2D- (AUC 0.67) and TVI-strain (AUC 0.71) for the diagnosis of CAD. The accuracy of WMS (75%) for diagnosis of CAD per patient was similar to 2D-SR (69%) and TVI-SR (74%). The accuracy of 2D-SR and TVI-SR at peak stress was 78 vs. 79% (P = NS) for LAD, 67 vs. 73% (P = NS) for LCX, and 59 vs. 74% (P = 0.008) for RCA disease. CONCLUSION: Measurement of speckle tracking strain during DSE is feasible and similar in accuracy to TVI-strain in the anterior, but not in the posterior circulation.