Diploid and triploid Eastern oysters, Crassostrea virginica, were tested at 3 sites characterized by low or moderate salinity regimes in the Virginia part of the Chesapeake Bay from November 2005 through October 2007. Both diploid and triploid cultures were replicated 3 times by producing separate spawns from different broodstock. Ploidy had a generally consistent effect on the performance of C. virginica at the 3 test sites. At the end of the study, in October 2007, and across all sites, triploid oysters had lower cumulative mortality than diploids (-34%), and greater shell height ( 25%), whole weight ( 88%), and yield ( 152%). as well as a higher proportion of market-size oysters ( 114%) than diploids. Both diploids and triploids were similarly infected by Perkinsus marinus and, to a lesser extent, by Haplosporidium nelsoni. In a closer look, growth parameters (shell height growth, whole weight, yield, and percentage of marketable oysters) were always higher in triploids than in diploids regardless of the parental source, strongly supporting the superior advantage of triploids. Similar results were obtained for cumulative mortality, but to a lesser extent as a result of the large variation in mortality for both diploid and triploid cohorts among sites, as well as a significant site-by-cohort interaction. Our report is the first clear illustration of variation for the cumulative mortality exhibited among different spawns in triploids, and comes with the lesson that care must be taken in experiments in which the goal is to test the effect of ploidy on this trait. Our results support the notion that selective breeding programs to reduce mortality, coupled with triploid production to increase growth, can further optimize yield. The best-performing replicate spawn had 80% survival after 2.5 y, and reached an average shell height of 92 mm, weighing 142 g.