A number of studies carried out in recent years have shown the presence of a wide range of contaminants in the Venice Lagoon. It is important to have a good understanding of the ecological quality of Venice Lagoon sediments in order to 1) define and locate areas where a threat to the environment is present and therefore an intervention is needed (i.e., in situ assessment and management); and 2) define sustainable and environmentally correct ways of managing sediments that are to be dredged for navigational purposes or in relation to other interventions (i.e., ex situ management). This study reports on a critical comparison of chemical quality of sediments in Venice Lagoon and its subregions. Data on the Venice Lagoon were compiled from several studies conducted during the past decade on surface sediment contamination; temporal variation and risks for contaminants at depth were not addressed. The comparison of observed pollutant concentrations with local and internationally used sediment quality guidelines (SQGs) was used as a tool to benchmark different sites and for a tier I (screening) ecological risk assessment. Meaning and relevance of a number of SQGs are discussed, together with the options available for carrying out the comparison with sediment data. The screening of the Venice Lagoon sediment quality is discussed from a risk-assessment perspective and appropriate values for use in an in situ-ex situ management framework are suggested. Although there were some differences depending upon which specific SQGs were applied, different SQGs provided the same general picture of screening risk in Venice Lagoon: Although there are geographic differences, median levels for several contaminants in surface sediments exceeded a number of SQGs. Many contaminants exceed threshold effects SQGs, and Hg exceeds probable effects SQGs in most sub-basins except the southern Lagoon. Venice Lagoon south has the lowest screening risk levels, Venice Lagoon central/north has the highest (and is nearest to the Porto Marghera and Venice City Canals sites). Ranges are high in all areas, therefore any remedial or disposal decision should use site-specific data.