Abstract: Background - Repeatable and reliable measurements of the feline left ventricular (LV) wall are difficult to obtain due to irregularities of the endocardium, false tendons, asymmetric hypertrophy, and prominent papillary muscles. Contrast-enhanced echocardiography (C-Echo) is utilized in human medicine to optimize measurements of the LV wall and is more accurate, repeatable, and reliable than standard echocardiography (S-Echo). Hypothesis/Objectives - Compare C-Echo and S-Echo measurements of LV wall thickness (LVWT) and determine repeatability, reproducibility, and reliability for each modality. Animals - Fifty client-owned cats; LVWT < 5 mm (n=30), LVWT 5 – 6 mm (n=8), and LVWT > 6 mm (n=12). Methods - Prospective observational study. All cats underwent S-Echo by two observers and C-Echo by one observer after intravenous injection of 0.2-0.4 mL contrast agent (Lumason, sulfur hexafluoride lipid-type-A microspheres). Methods were compared using Bland-Altman and Passing-Bablok regression. Inter- and intraoperator reproducibility were quantified using intraclass correlation (ICC) and 95% repeatability/reproducibility coefficients (RC). Results - Method comparison between S-Echo and C-Echo demonstrated significant differences in LVWT for all segments. Globally, the median difference in LVWT between S-Echo and C-Echo was 0.56 mm (range, -1.4-4.9 mm; P< 0.0001) and regression showed a proportional bias of 1.21 mm (95% CI 1.11-1.32). Excellent intra- and interoperator reproducibility was observed for S-Echo and C-Echo based on ICC 0.89-0.97 and 0.87-0.94, respectively with lower RCs for C-Echo (0.28mm-0.61mm) compared with S-Echo (0.89mm-1.03mm). Conclusions and Clinical Importance - Compared with S-Echo, C-Echo yields lower LVWT measurements, excellent visualization of the LV wall, and superior repeatability and reproducibility.