We estimated the additive genetic variation and heritability of vibrio resistance in the clam Meretrix petechialis by using four statistical models to analyze data from challenge tests. A total of 2541 individuals from 23 full-sib families were infected with V. parahaemolyticus, which causes vibriosis in clams. The daily mortality was recorded, and the experiment was terminated after 18days, when the death rate fell to approximately zero. The overall mortality of clams approached 60% at the end of the test, and significantly different survival rates were observed among families, e.g., six full-sib families suffered 80–97% mortality, whereas 9 families showed only 17–48% mortality. Variance components were analyzed using cross-sectional models, and moderate to high heritability was estimated for vibrio resistance in both the linear model (0.31–0.32) and the sire-dam threshold model (0.53) but not in the animal threshold model (0.006). Estimated breeding values (EBVs) of the two types of models showed high and positive correlations (0.92–0.99), which meant that these models showed similar utility for predicting breeding value. These results indicate that an efficacious and reliable challenge method of infecting M. petechialis clams with V. parahaemolyticus was achieved and that vibrio resistance in clam might be genetically improved through selective breeding.The clam Meretrix petechialis is an important commercial cultured mollusc species in China. Our results provided a reliable challenge method of infecting clam with V. parahaemolyticus and estimated basic genetic evaluation for vibrio resistance, which should be useful for the design and operation of a practical vibrio resistance selective breeding program in the clam M. petechialis.