Effective population size (Ne) is an important concept in population genetics as it dictates the rate of genetic change caused by drift. Ne estimates for many marine populations are small relative to the census population size. Small Ne in a large population may indicate high reproductive variance or sweepstakes reproductive success (SRS). The eastern oyster (Crassostrea virginica) may be prone to SRS due to its high fecundity and high larval mortality. To examine if SRS occurs in the eastern oyster, we studied Ne and genetic variation of oyster populations in Delaware Bay. Adult and spat oysters were collected from five locations in different years and genotyped with seven microsatellite markers. Slight genetic differences were revealed by Fst statistics between the adult populations and spat recruits, while the adult populations are spatially homogeneous and temporally stable. Comparisons of genetic diversity and relatedness among adult and spat samples failed to provide convincing evidence for strong SRS. Ne estimates obtained with five different methods were variable, small and often without upper confidence limits. For single sample collections, Ne estimates for spat (140–440) were consistently smaller than that for adults (589–2,779). Analysis of pooled adult samples across all sites suggests that Ne for the whole bay may be very large, as indicated by the large point estimates and the lack of upper confidence limits. These results suggest that Ne may be small for a given spat fall, but the entire adult population may have large Ne and is temporally stable as it is the accumulation of many spat falls per year over many years