Background <p>The combination of vancomycin and ceftazidime antibiotics in bone cement remains a viable option for treatment of periprosthetic joint infections (PJI). This study evaluates the impact of these antibiotics on the biomechanical characteristics of the bone cement.</p> Methods <p>Bone cement specimens containing varying dosages of vancomycin and ceftazidime were prepared. Their properties were assessed to examine the effect of increasing antibiotic concentrations on the biomechanical properties of the cement. All groups underwent axial compression and three-point bending tests using the Instron^® 3365 Material Testing System (Norwood, MA).</p> Results <p>The control group had an axial compression strength of 105.60 ± 14.77 MPa and a three-point bending strength of 63.75 ± 8.98 MPa. The highest axial compression and three-point bending strengths were observed with the combination of 2 g vancomycin and 2 g ceftazidime, which had an axial compression strength of 78.24 ± 11.04 MPa and a three-point bending strength of 43.78 ± 22.57 MPa. The lowest strengths were observed with the 4 g vancomycin and 4 g ceftazidime formulation, which had an axial compression strength of 23.98 ± 5.93 MPa and a three-point bending strength of 9.76 ± 2.35 MPa. The mechanical strength of the bone cement decreased as the antibiotic concentration increased.</p> Conclusion <p>The strength of bone cement diminishes with an increase in antibiotic dose. Based on our findings, the optimal dosage to prevent bone cement fracture is a combination of 2 g vancomycin and 2 g ceftazidime.</p>