The purpose of the research was to collect all available data on the concentration of heavy metals (Cd, Pb, Hg, As) in the Mediterranean mussel Mytilus galloprovincialis and to analyze samples from three different locations, including the northern, middle and southern Adriatic, over a period of four years: Mali Ston Bay, Šibenik channel and Lim Bay in 2018 and 2022. Also, a systematic review and comparison with existing data on the concentration of heaviest metals in the Adriatic was conducted. Considering the toxicity and carcinogenicity of the heaviest metals, their concentration in shellfish represents a health risk. Mytilus galloprovincialis samples were collected and analyzed, and the concentration of heavy metals was determined using hydride generation atomic absorption spectrometry and graphite furnace atomic absorption spectrometry techniques. Analysis of heavy metal concentration revealed spatial and temporal variations. In Lim Bay, lead, mercury and arsenic concentrations were higher in 2022 compared to 2018, while cadmium levels decreased. Similar trends were recorded in the Šibenik Canal, with increased lead and arsenic concentrations but decreased cadmium and mercury levels in 2022. In Mali Ston Bay, the concentrations of all heavy metals decreased in 2022 compared to 2018, while no concentrations exceeding the legally prescribed values were recorded. In conclusion, M. galloprovincialis from the examined locations in the Adriatic Sea do not pose a danger to the health of consumers in terms of the concentration of heavy metals, anyhow continuous monitoring and further research is needed to ensure the safety and quality of shellfish in the food chain.