Purpose Copal® spacem is a new PMMA bone cement for fabricating spacers. This study compares elution of gentamicin, elution of vancomycin, and compressive strength of Copal® spacem and of Palacos® R+G at different vancomycin loadings in the powder of the cements. We hypothesized that antibiotic elution of Copal® spacem is superior at comparable compressive strength. Methods Compression test specimens were fabricated using Copal® spacem manually loaded with 0.5 g gentamicin and additionally 2 g, 4 g, and 6 g of vancomycin per 40 g of cement powder (COP specimens) and using 0.5 g gentamicin premixed Palacos® R+G manually loaded with 2 g, 4 g, and 6 g of vancomycin per 40 g of cement powder (PAL specimens). These specimens were used for determination of gentamicin and vancomycin elution (in fetal calf serum, at 22°C) and for determination of compressive strength both prior and following the elution tests. Results Cumulative gentamicin concentrations (p < 0.005) and gentamicin concentration after 28 days (p ≤ 0.043) were significantly lower for COP specimens compared to PAL specimens. Cumulative vancomycin concentrations were significantly higher (p ≤ 0.043) for COP specimens after the second day. Vancomycin concentrations after 28 days were not significantly higher for the Copal specimens loaded with 2 g and 4 g of vancomycin. Compressive strength was not significantly different between COP specimens and PAL specimens before elution tests. Compressive strength after the elution tests was significantly lower (p = 0.005) for COP specimens loaded with 2 g of vancomycin. Conclusion We could not demonstrate consistent superior antibiotic elution from Copal® spacem compared to Palacos® R+G for fabricating gentamicin and vancomycin loaded spacers. The results do not favor Copal® spacem over Palacos® R+G for the use as a gentamicin and vancomycin biantibiotic-loaded spacer.