Abstract. Background: the treatment of infected non-union to allow for bony healing following orthopedic surgery remains a challenge. Antibiotic-impregnated calcium sulfate (AICS) is an effective vehicle for antibiotic delivery, but its efficacy in treating infected non-union in the setting of trauma and fracture remains unclear. Methods: this systematic review analyses nine studies from 2002 to 2022 that investigated AICS as a local antibiotic delivery system for cases of fracture-related infection and infected non-union. Results: in total, 214 patients who received AICS were included in this review. Of these patients, there were 154 cases of infected non-union or fracture-related infection. Across all studies analyzed, patients treated concurrently with AICS and systemic antibiotics experienced a 92.9 % rate of bony union and a 95.1 % rate of infection eradication. In addition, 100 % of the 13 patients who were treated with AICS alone experienced eradication of infection and successful bony union. Conclusion: AICS is an effective method of antibiotic delivery with a low risk profile that results in high rates of bony union and infection eradication even when used in the absence of systemic antibiotics.