Strain (epsilon) rate (SR) imaging and left ventricular (LV) opacification with intravenous (IV) contrast both potentially decrease operator dependency in interpretation of stress echocardiography. The aim of this study was to evaluate whether contrast present during tissue velocity imaging (TVI) significantly affected measurements of velocity, epsilon, and SR. Secondly, we sought to evaluate whether increased scan line density improved feasibility of simultaneous TVI and contrast echocardiography. The 4-chamber LV view in 15 healthy volunteers and 25 patients was acquired at rest before and after IV injections of contrast using: (1) conventional TVI; (2) LV opacification with standard TVI added; and (3) modified LV opacification with doubled TVI line density. Velocity, SR, and epsilon curves, along with peak systolic velocity, peak systolic SR, and end-systolic epsilon, were assessed from midwall segments. IV contrast significantly reduced feasibility of TVI with standard settings, giving noisy data for SR and epsilon, particularly in the septum. Absolute values of peak systolic SR and end-systolic epsilon from adequately shaped curves were significantly higher with contrast compared with baseline. However, increased TVI line density significantly improved feasibility of velocity traces with contrast and decreased the level of noise in SR and epsilon. Furthermore, higher line density improved agreement between peak systolic velocity, peak systolic SR, and end-systolic epsilon measured with contrast, and corresponding precontrast values from the conventional TVI setting. SR imaging was not feasible performed with IV contrast during conventional TVI settings, and we do not recommend the clinical use of this combination. Increased TVI line density made velocity curves with contrast feasible and resulted in less noisy SR and epsilon curves, but variability in SR and epsilon measurements with contrast is still too high for clinical use.