The emergency of antibiotic-resistant bacteria and their wide spread has posed a worldwide threat to public health, and traditional antibiotics are gradually overwhelmed by infectious bacteria. Herein, we report an efficient and economical strategy to construct antimicrobial polymers with net cationic component and hyperbranched architecture, which exhibit highly selective toxicity toward bacteria over human cells. To this aim, cationic poly(aminoethyl acrylate) (PAEA) without hydrophobicity is chosen for low hemolysis activity and targeting the negative bacterial membranes, and hyperbranched architecture is introduced to solve the dilemma of low antimicrobial activity. Long-subchain hyperbranched PAEA (lhb-PAEA) samples kills > 99.99% gram-negative Escherichia coli and > 98% gram-positive Staphylococcu aureus at the dose of <= 4 mu g/mL. Moreover, lhb-PAEA samples exhibit great biocompatibility, for the hemolysis percentage was <= 35% even at the high dose of 1024 mu g/mL. Thus, enhanced antimicrobial activity, reduced hemolytic toxicity, the feasible and low-cost production are achieved for lhb-PAEA as antimicrobial agents. (C) 2016 Wiley Periodicals, Inc.