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Mass mortalities of cultured triploid Crassostrea virginica in late spring, or "triploid mortality," have been reported on farms in the Chesapeake Bay since 2012. Typical causes, such as disease or poor husbandry, were not responsible, and mortalities occurred without clear signs of biological or physical stressors. Previous comparisons of the effects of genetic origin on triploid mortality have been uncontrolled, initiating this investigation of the effect of brood stock source and ploidy on triploid mortality. Four triploid and four diploid crosses, produced by crossing different combinations of brood stock of Virginia, Louisiana, and Maine origin in early 2015, were tested at four commercial oyster farms in Virginia throughout 2016. From February to November, oysters from all crosses and sites were regularly sampled, and growth (shell height), condition (meat weight), and pathology were monitored, as were environmental conditions. Compared to diploids made from Virginia brood stock, diploids with Maine genetic origin had high mortality, and diploid Virginia-Maine hybrids exhibited mid-parent heterosis. A triploid mortality event occurred in late spring at only one site and only affected the triploid crosses. Evidence for substantial disease pressure from Haplosporidium nelsoni or Perkinsus marinus or of especially stressful environmental conditions based on temperature, salinity, pH, and dissolved oxygen was absent during the triploid mortality event. At 18 months, shell height was similar in the diploids and triploids with the most similar genetic origin. Triploids maintained meat weight through the summer, while meat weight in diploids dropped sharply. Triploids may be especially susceptible to late spring mortality events in the Chesapeake Bay, which justifies their classification as "triploid mortality" and warrants further investigation on traits in triploids that may affect susceptibility. • Mass mortality occurred in late spring without evidence of disease or stressful conditions. • Triploids of heterogenous genetic lineage underwent similar mass mortality. • Locally adapted diploids had low mortality during the mass mortality event. • Diploid Virginia-Maine hybrids exhibited heterosis for mortality. [ABSTRACT FROM AUTHOR]