Major crossmatch testing can help identify immunologic incompatibilities between blood donors and recipients; however, there are limited studies describing the accuracy of point-of-care crossmatch tests. The first aim of this study was to determine if a gel-based, point-of-care major crossmatch method (GEL-CM), without antiglobulin-enhancement, could accurately detect compatible and incompatible donor-recipient pairings, using an antiglobulin-enhanced laboratory-based major crossmatch method (LAB-CM) as the reference standard. The second aim was to describe the incidence of, and risk factors for, major crossmatch incompatibility in cats. Nineteen previously-transfused cats and 32 transfusion-naïve cats, representing 132 unique donor-recipient pairings, were included in this study. Both LAB-CM and GEL-CM tests were performed for most parings. There was poor agreement between the LAB-CM and GEL-CM results (kappa = 0.111; 95% confidence interval [CI], -0.093 to 0.314). Transfusion-naïve cats had incompatibility rates of 3% and 6% using LAB-CM and GEL-CM, respectively; previously-transfused cats had incompatibility rates of 32% and 26% using LAB-CM and GEL-CM, respectively. History of previous transfusion was the only identified cat risk factor for an incompatible LAB-CM (odds ratio [OR], 31.0; 95% CI, 3.77-254.98; P = 0.0019) and GEL-CM (OR, 5.7; 95% CI, 1.72-19.20; P = 0.0054). Further studies are needed to determine if GEL-CM can detect clinically-relevant immunologic incompatibilities that would result in transfusion reactions. Major crossmatch testing is of greater importance in cats that have previously received a transfusion.