Antibiotic beads have been used as a drug delivery system for the treatment of various surgical infections. In this study, the copolymer 50:50 poly(DL-lactide):co-glycolide was mixed with vancomycin powder and hot compressing molded at 55° C to form five types of biodegradable antibiotic beads. The beads were placed in 1 mL of phosphate buffered saline and incubated at 37° C. The phosphate buffered saline was changed daily, and the removed buffer solutions were stored at −70° C until the antibiotic concentration in each sample was determined by high performance liquid chromatography system assay. The concentration of vancomycin in each sample was well above the breakpoint sensitivity concentration (the antibiotic concentration at the transition point between bacterial killing and resistance to the antibiotic) for more than 32 days. The release was most marked during the first 48 hours. All copolymer 50:50 poly(DL-lactide):co-glycolide biodegradable beads released high concentrations of the antibiotics in vitro for the time needed to treat bone infections (4 to 6 weeks). The diameter of the sample inhibition zone ranged from 6.5 mm to 10 mm, and the relative activity of vancomycin ranged from 12.5% to 100%. Copolymers with low heat of formation temperatures are required for making a controlled release system to prevent antibiotic decomposition, which occurs when using the hot compressing molded method. The rate and duration of release from the antibiotic beads can be adjusted by varying the diameter of the beads. This offers a convenient method to adjust the release rate to meet the specific antibiotic requirements for different patients.