Genetic studies of several marine species with high fecundity have produced “tiny” estimates (≤10−3) of the ratio of effective population size (Ne) to adult census size (N), suggesting that even very large populations might be at genetic risk. A recent study using close-kin mark-recapture methods estimated adult abundance at N ≈ 2 × 106 for southern bluefin tuna (SBT), a highly fecund top predator that supports a lucrative (~$1 billion/year) fishery. We used the same genetic and life history data (almost 13,000 fish collected over 5 years) to generate genetic and demographic estimates of Ne per generation and Nb (effective number of breeders) per year and the Ne/N ratio. Demographic estimates, which accounted for age-specific vital rates, skip breeding, variation in fecundity at age, and persistent individual differences in reproductive success, suggest that Ne/N is >0.1 and perhaps about 0.5. The genetic estimates supported this conclusion. Simulations using true Ne = 5 × 105 (Ne/N = 0.25) produced results statistically consistent with the empirical genetic estimates, whereas simulations using Ne = 2 × 104 (Ne/N = 0.01) did not. Our results show that robust estimates of Ne and Ne/N can be obtained for large populations, provided sufficiently large numbers of individuals and genetic markers are used and temporal replication (here, 5 years of adult and juvenile samples) is sufficient to provide a distribution of estimates. The high estimated Ne/N ratio in SBT is encouraging and suggests that the species will not be compromised by a lack of genetic diversity in responding to environmental change and harvest.