The objective of this study was to carry out a critical comparison of data on the screening quality of surface sediments in Venice Lagoon (VL; main lagoon and its subbasins, Porto Marghera [PM], and Venice City Canals) and in other transitional and coastal ecosystems with various levels of human impact (urbanization and industrialization). To put VL in terms of reference and industrialized sites in the region, case studies were selected from the North Adriatic Region; to gain insight into how VL sediments compared to transitional areas throughout the world, case studies also were selected from a number of regions internationally. In order to compare regional levels of contamination, statistically processed sediment contaminant levels within a region (minimum, maximum, mean, and median), not individual sample values, are compared. The screening quality (relative to a variety of sediment quality guidelines) and the drivers of screening risk (based upon contaminant mixtures) of the VL sediments and other coastal and transitional sites are compared and discussed. The VL sediments have hazard quotients on the low end of the range typical of moderately urbanized and industrialized sites and higher than background conditions among the case studies reviewed. The Hg levels in the VL were generally higher than at other sites, and other contaminants were either equivalent or lower. Although sediments have somewhat higher levels of some contaminants and lower levels of other contaminants in PM and Venice City (VC) canals, levels for most contaminants are comparable to case studies with high levels of anthropogenic impact. For many contaminants of interest, PM (and for some, VC) sediments have some of the highest levels of any case study reviewed. How PM and VC rank when compared to other highly industrialized sites depends upon how data are synthesized and how ranges are taken into account. Actual risk must be evaluated using a weight-of-evidence approach, because natural background levels and site-specific bioavailability will differ both regionally and internationally.