The northern quahog Mercenaria mercenaria, also known as the hard clam, is an important aquaculture species in the United States. Genetic and genomic studies in this species require a large set of genetic markers. In this study, microsatellite markers were developed from an enriched DNA library. Five hundred sixty-seven clones were sequenced, producing 337 microsatellite-containing sequences with di- (82.0%), tri- (7.8%), tetra- (7.8%), hexa- (1.1 %), hepata- (1.1%), and octanucleotide (0.2%) repeats. Sixty primer pairs were designed and screened in 24 clams from a wild population, of which 30 primer pairs showed good amplification and produced no more than 2 alleles per individual. The other 30 primer pairs either failed to amplify consistently or amplified multiple fragments. Of the 30 primer pairs with good amplification, 29 were polymorphic with allele numbers ranging from 3-21 per locus. The expected and observed heterozygosity ranged from 0.5381–0.9628 and from 0.0417– 0.9167, respectively. Fourteen of the 29 loci showed significant (P < 0.05 after Bonferroni correction) deviation from Hardy— Weinberg equilibrium, probably because of the presence of null alleles. Most of the microsatellite markers developed here should be useful for genome mapping and some for population genetics studies in this species.