Background: The wall motion score index (WMSI) is a surrogate for left ventricular ejection fraction (LV‐EF), which becomes unreliable in poor echo windows. The value of contrast LV opacification (LVO) for WMSI assessment is not well known. Objectives: We sought to compare interobserver agreement for WMSI and the correlation between the LVO‐WMSI and LV‐EF using two‐dimensional second harmonic (SH) and LVO echocardiography. Methods: The study comprised 100 consecutive patients (57 ± 13 years, 85% males). Two independent physicians assessed LV segmental quality and wall motion for both the SH and LVO studies according to a 17‐segment model. Systolic wall motion was defined as: normokinesia, hypokinesia (systolic inward endocardial motion <7 mm), akinesia, and dyskinesia. LV‐EF was assessed from the LVO images according to the biplane modified Simpson's method. Results: Of the 1,700 analyzed segments, 453 (26.6%) were poorly visualized with SH imaging, and 173 (10.2%) with LVO (P < 0.0001). The two observers agreed on segmental wall motion score in 1,299 segments (agreement 76%, Kappa 0.60) with SH imaging and in 1,491 segments (agreement 88%, Kappa 0.78) with LVO. Interobserver correlation (r2) was 0.86 for the SH‐WMSI and 0.93 for the LVO‐WMSI. The limits‐of‐agreement for interobserver LVO‐WMSI (mean difference –1.0%± 6.8%, agreement –14.6%, 12.6%) was lower than that for SH‐WMSI (mean difference –2.3%± 10.1%, agreement –22.5, 17.9). The LVO‐WMSI correlated well with LV‐EF (r2= 0.71). LV‐EF could be estimated according to the formula 1.01 – 0.32 × WMSI. Conclusion: Echo‐contrast improves interobserver agreement for wall motion scoring and the WMSI. The LVO‐imaged WMSI correlates well with LV‐EF. (Echocardiography 2011;28:575‐581)