A series of scale inhibitor copolymers modified with oxidized starch have been synthesized. The effects of content of monomer and initiator, reaction time, reaction temperature to inhibit calcium carbonate scale were studied by orthogonal experiment. The structure, thermal property and morphology of the copolymer were characterized by FT-IR, TGA and SEM. Using the static experiment method, the scale inhibition efficiency for CaCO3 scale was investigated. The experimental results showed that the scale inhibitor copolymer modified with oxidized starch had an excellent efficiency of scale inhibition, good tolerance of calcium and could be used in the high hardness water.