Three selected aquaculture strains of the commonly used hard clam, Mercenaria mercenaria (Linnaeus, 1758)—Massachusetts (MA), New Jersey (NJ), and South Carolina (SC)—were reared in a single hatchery. They were planted in replicate plots in Barnstable Harbor, MA, and Dry Bay, NJ, in spring 2008 and grown to market size. Growth, survival, and QPX (quahog parasite unknown) prevalence and severity were measured in fall 2008, spring 2009, and fall 2009. Growth was similar at both sites for the first summer, but during the second year growth was better in Massachusetts. Overall survival was better for all strains in New Jersey when compared with Massachusetts. Survival of strains in New Jersey was 53.4% and 34.8% for NJ and MA, respectively, closely followed by those in Massachusetts (41.8% and 26.2% for NJ and MA, respectively). Strains from SC seed had the highest prevalence and severity of QPX and the lowest survival (36% and 6.6% in New Jersey and Massachusetts, respectively). Infections with QPX were low at both sites, but this study confirms earlier work indicating that QPX infection rates appear to be strain specific, with strains of southern origin being more susceptible than those of northern origin. Our study also supported anecdotal reports that QPX disease is more severe in Massachusetts than in more southern sites where it has been found. As in most previous field studies, we found that although mortality was correlated with QPX levels, it was considerably higher than infection prevalence would indicate, which suggests that strain interactions with stressful environmental conditions or unidentified factors may be also involved in mortality.