BACKGROUND: Blood transfusions are performed frequently in goats, but crossmatches are rarely performed. HYPOTHESIS/OBJECTIVES: Determine differences in the frequency of agglutination and hemolytic crossmatch reactions between large and small breed goats. ANIMALS: Healthy adult goats, 10 large and 10 small breed. METHODS: Two hundred eighty major and minor agglutination and hemolytic crossmatches: 90 large breed donor to large breed recipient (L-L), 90 small breed donor to small breed recipient (S-S), 100 large breed donor to small breed recipient (L-S). A linear mixed model with treatment group (L-L, S-S, L-S) as a fixed effect and individual crossmatch as a random effect was used to identify variations in reaction frequency among groups and individuals. RESULTS: Frequency of major agglutination reactions for L-L, S-S, and L-S were 3/90 (3.3%), 7/90 (7.8%), and 10/100 (10.0%), respectively. Frequency of major hemolytic reactions for L-L, S-S, and L-S were 27/84 (32.1%), 7/72 (9.7%), and 31/71 (43.7%). Individual pairings and groupings had no effect on agglutination reactions. Individual pairings had no effect on the frequency of hemolytic reactions. For major hemolytic crossmatches, pairwise comparisons identified higher frequencies of reactions when comparing L-L to S-S (P = .007) and L-S to S-S (P < .001). CONCLUSION AND CLINICAL IMPORTANCE: Goats experience increased frequencies of hemolytic reactions compared to agglutination. Significant increases in hemolysis were seen between large breed donors and small breed recipients, compared to small breed pairings. Additional studies are required to determine correlations between crossmatches and transfusion reactions.