The adverse effect of seafood consumption on human health is related to the bioaccessibility in contrast with the total heavy metal level in the tissues. In this study, bioaccessibility of Cd, Cr, Cu, Mn, Ni, Pb, and Zn in Mediterranean mussel (Mytilus galloprovincialis Lamarck, 1819) edible soft tissues collected along the southern Black Sea coast were investigated using in vitro digestion model. Total Pb concentration in the tissues was found to be higher than the maximum permissible limits set by European Commission. The bioaccessibility of metals in the tissues was found to be decreased in the order: Ni (83.11%) > Cu (80.47%) > Zn (76.86%) > Cd (73.32%) > Mn (69.11%) > Pb (61.07%) > Cr (58.44%). While significant positive linear regression was observed between total and bioaccessible concentrations for Mn, Pb, and Ni, significant negative linear regression was found for Cd (p < .05). The hazard quotients (HQ) calculated using bioaccessible amount were detected lower than the limit (HQ <1), which may not pose a potential hazard to humans reported by US Environmental Protection Agency. In sum, mussel consumption from sampling sites may cause a potential risk concerning human health especially for Cd and Pb in case of increased portion sizes.