The fouling of hard substrates by zebra mussels (Dreissena sp.) in freshwater ecosystems is a persistent problem which calls for antifouling treatments being fully efficient, long-lasting, and environmentally safe. The present study assessed the potential toxicological impact and the effectiveness of an elastomer-based coating containing salts that would make surfaces repulsive to zebra mussel attachment. Laboratory testing using standard analytical methods for water and wastewater, and a battery of six bioassays confirmed that the leachates from the coating exhibited no toxic response suggesting its safety to the receiving environment. In situ experiments using multi-plate collectors indicated that biofouling by zebra mussels and sponges on coated surfaces was effectively reduced by up to 97% over one growing season. Effectiveness of the coating was slightly less (82%) during the second growing season. Results suggested that the repulsive effect would be due to the presence of salts within the elastomer-based coating affecting both zebra mussels and other freshwater organisms. Saltwater experiments indicated that the coating was totally ineffective to prevent biofouling in marine environments. In addition of being environmentally safe to use, results suggested that the coating can be an effective antifouling product for submerged structures in freshwater environments.