Supplying fresh water has become an important environmental and economic issue. Desalination with reverse osmosis (RO) represents an effective solution to meet the challenges of cleaning brackish water and seawater for drinking and industrial purposes. The principal problem of RO plant operation is the precipitation of low soluble salts (scaling). There are some well-known techniques to reduce scaling; one of the most widespread is antiscalant dosing. In this study, 11 samples of new prototype chemicals based on co-polymers of acrylic and methacrylic acids, polyaspartic acid, maleic anhydride and different cross-linking agents is tested. A wide range of commercial phosphorus-based and green inhibitors were used as reference antiscalants. The testing procedure included circulation experiments on a RO laboratory unit with continuous concentration of feed water – tap water and model solution with elevated hardness. The amount of calcium carbonate accumulated in the membrane module was determined and the inhibitor efficiency was calculated. The best results were obtained for scale inhibitors based on polyaspartic and (poly)acrylic acids. The most promising was the reagent based on a mixture of polyaspartate and nitrilotrimethylphosphonic acid.