OBJECTIVE To: (1) assess the frequency of crossmatch incompatibility in naïve feline blood transfusion recipients using two crossmatching methods, (2) measure the effect of crossmatch incompatibility on change in packed cell volume following transfusion, (3) assess the frequency of acute transfusion reactions and errors in blood transfusions in cats and (4) assess the impact of crossmatch incompatibility on the likelihood of transfusion reactions. METHODS Cats being administered a first AB-matched transfusion in a veterinary teaching hospital were prospectively recruited for this observational study. A slide agglutination method and a commercial test were both used for major and minor crossmatching. We measured increase in packed cell volume at 12 hours after transfusion relative to the mass of red blood cells given per recipient bodyweight and recorded transfusion reactions. RESULTS A total of 101 cats was included. Crossmatch incompatibility was common using the slide agglutination method (27% and 10% major and minor incompatibility, respectively), but less common with the commercial test (major and minor incompatibility both 4%). Crossmatch incompatibility with any method was not associated with less effective transfusion in terms of change in packed cell volume. Transfusion reactions occurred in 20 cats, most commonly febrile non-haemolytic transfusion reactions (n = 9) and haemolytic transfusion reactions (n = 7). The commercial test appeared to be most specific for predicting haemolytic transfusion reactions. CONCLUSIONS Transfusion reactions were fairly common but not associated with increased mortality. Use of crossmatch-compatible blood did not lead to a greater increase in PCV at 12 hours. The commercial test may predict a haemolytic transfusion reaction.