This study focuses on the solution antimicrobial effectiveness of a novel class of copolyoxetanes with quatemary ammonium and PEG-like side chains. A precursor P [(BBOx-m)(ME2Ox)) copolyoxetane was prepared by cationic ring-opening copolymerization of 3((4-bromobutoxy)methyl)-3-methyloxetane (BBOx) and 34(2-(2-methoxyethoxy)ethoxy)methyl)3-methyloxetane (ME2Ox) to give random copolymers with 14-100 (m) mol % BBOx. Reaction of P[(BBOx-m)(ME2Ox)] with dodecyl dimethylamine gave the corresponding quaternary P[(C12-m)(ME2Ox)] polycation salts, designated C12-m, as viscous liquids in 100% yield. BBOx/ME2Ox and C12/ME2Ox ratios were obtained by H-1 NMR spectroscopy. C12-m molecular weights (M-n, 3.5-21.9 kDa) were obtained from 1H NMR end group analysis. DSC studies up to 150 degrees C showed only thermal transitions between -69 and -34 degrees C assigned to T-g values. Antibacterial activity for the C12-m copolyoxetanes was tested by determining minimum inhibitory concentrations (MICs) against Gram(+) Staphylococcus aureus and Gram() Escherichia coli and Pseudomonas aeruginosa. MIC decreased with increasing C12 mol percent, reaching a minimum in the range C12-43 to C12-60. Overall, the antimicrobial with consistently low MICs for the three tested pathogenic bacteria was C12-43: (bacteria, MIC, mu g/mL) E. coil (6), S. aureus (5), and P. aeruginosa (33). For C12-43, minimum biocidal concentration (MBC) to reach 99.99% kill in 24 h required 1.5 x MIC for S. aureus and 2 x MIC for E. coil and P. aeruginosa. At 5 x MIC against a challenge of 10(8) cfu/mL C12-43 kills >= 99% S. aureus, E. colt, and P. aeruginosa within 1 h. C12-m copolyoxetane cytotoxicity toward human red blood cells was low, indicating good prospects for biocompatibility. The tunability of C12-m copolyoxetane compositions, effective antimicrobial behavior against Gram(+) and Gram() bacteria, and promising biocompatibility offer opportunities for further modification and potential applications as therapeutic agents.