Objective: The usage of antibiotic-impregnated polymethylmethacrylate (PMMA) beads is regarded as the gold standard for local antibiotic delivery. However, the relatively new antibiotic-impregnated collagen sponge has multiple advantages over it. The objective of this study is to compare the measurable effects between gentamicin-impregnated collagen sponge and gentamicin-impregnated (PMMA) beads in patients with osteomyelitis.Methods: This is a case–control study which involved 60 patients who were diagnosed with osteomyelitis between January 2014 and June 2015, and underwent first surgical debridement with application of either gentamicin-impregnated collagen sponge (n=28) or gentamicin-impregnated PMMA beads (n=32). The numbers of debridement, trend of blood parameters, duration of hospitalization, and total duration of systemic antibiotic therapy needed to be completed were reviewed from the patients’ file.Results: A total of 53 patients of 60 were diagnosed with osteomyelitis of the lower limbs, while the remaining seven were involving the upper limbs. The gentamicin-impregnated collagen sponge group has significant lower reoperative rate (p<0.05) and also significant reduction of total white cell count in 6 weeks (p<0.05). The two groups showed no statistical difference in regard of duration of hospital admission, duration of systemic antibiotic therapy completed, and the reduction of C-reactive protein at 6 weeks post-debridement.Conclusion: This study reiterates the efficacy of gentamicin-impregnated collagen sponge that results in lower reoperative rate as compared to conventional gentamicin-impregnated PMMA beads.