Combining two antibiotics in antibiotic-loaded bone-cement is common in clinical practice. As the effect this has on elution characteristics is unknown, an in vitro quantitative elution study was carried out. Three groups of five antibiotic-loaded cement disks were prepared and placed in individual saline baths for 5 weeks. The elution of tobramycin from the disks in the study group (containing 2.4 g tobramycin and 1.0 g vancomycin per 40-g packet of Palacos-R cement powder [Smith & Nephew Orthopaedics, Memphis, TN]) was increased by 68% over that of the tobramycin control disks (2.4 g tobramycin only) (P = .024). The release of vancomycin from the study group disks was increased by 103% over the vancomycin control disks (1.0 g vancomycin only) (P = .007). Combining two antibiotics in bone-cement improves elution of both antibiotics in vitro and may translate into enhanced elution in vivo.