Biodegradable, negatively charged, branched polyesters, namely, poly(vinyl sulfonate-covinyl alcohol)-graft-poly(D,L-lactic-coglycolic acid), abbreviated as P(VS-VA)-g-PLGA, were synthesized by ring-opening polymerization using sulfonate-modified poly(vinyl alcohol) backbones as a platform for cationic drug delivery systems. The structures of sulfonate-modified backbones and. the graft polyesters were characterized by NMR, FT-IR, GPC-MALLS, DSC, and viscosity measurements. By controlling the degree of sulfonate substitution of the backbone and the feed ratio of the backbone to the monomer, graft polyesters with different degrees of sulfonate substitution and different branch lengths were obtained. The random copolymer structure of PLGA and the successful grafting of PLGA to the P(VS-VA) backbone were confirmed by COSY NMR experiments. In vitro degradation studies demonstrated that the increased sulfonate substitution leads to a faster degradation rate; half-lives as fast as 8 days were observed. Nanoparticles were prepared from these amphiphilic graft copolymers by a solvent displacement technique and were characterized by particle size, polydispersity, zeta potential, and SEM. These novel biodegradable polyesters are promising candidates as negatively charged polyelectrolyte platforms for cationic drug delivery systems.