Prosthetic bone and joint infections are difficult to treat with varying levels of success with standard therapy. Synthetic calcium sulfate carrier, to which specific antibiotics can be added, can be utilized as an alternative drug delivery system in these cases. We have reviewed clinical outcomes using commercially available pure synthetic calcium sulfate dissolvable beads (Stimulan) loaded with antibiotics in 143 patients undergoing orthopedic surgery for prevention and treatment of joint infection. Stimulan was added after standard surgical procedure in cases of: (1) Established infections, (2) Second stage of previously infected patients, or (3) High risk of infection. The purpose of this study was to (1) Evaluate the efficacy of Stimulan for eradicating the infection in patients with established infection, and (2) To study the efficacy of Stimulan for preventing infection in previously infected and healed, or high-risk group of patients. Established orthopedic surgical procedures (such as debridement, liner exchange, one-stage or two-stage revision surgery, or culture-specific systemic antibiotic therapy) were carried out to treat infection, and Stimulan was added in the medullary canal and soft tissue. In addition, postoperative infection and other complications were recorded. This prospective study data showed postoperative wound drainage in 4.9% and infection in 9.1% of total patients. Success rate after the use of Stimulan was 84.9% for established infected patients, 90.9% for previously infected patients, and about 97% for high-risk group patients. Based on the results of this study, we conclude that Stimulan is an acceptable novel drug delivery system for local antibiotic in septic or aseptic standard orthopedic surgeries. Moreover, postoperative infection rate was lower than any other antibiotic delivery system or drugs used before. Stimulan is also effective as a preventive measure for infection-prone patients.