Objective. The aim of this meta-analysis is to evaluate the effect of withholding antibiotics prior to obtaining a bone biopsy in the diagnosis of osteomyelitis. Methods. Literature searches on Scopus, PubMed, and Google Scholar were performed with the input antibiotic, bone, biopsy, osteomyelitis, and prior both separately and together, though initially as a combination, as key words for all study types in the English language published up until July 2018. The initial combination search (and subsequent additional search of the references) yielded 924 related articles, which ultimately resulted in 12 articles with adequate data for analysis. Data were analyzed using an inverse variance method to determine the weight of the studies in a random effects model, pooling the data for odds ratios (OR) and heterogeneity. Bias risk was determined with the Quality Assessment of Diagnostic Accuracy Studies 2 system. Results. Of the 12 studies, 8 failed to demonstrate that antibiotics administered prior to bone biopsy have an effect on culture yield, while 4 reported a significant effect on culture yield. The total weighted OR for all studies was 2.02 (95% confidence interval [CI], 0.94–4.36; P = .04) and the prediction interval was 0.17–23.63. When vertebral osteomyelitis (VO) and nonvertebral osteomyelitis (NVO) articles were evaluated separately, the VO OR was 2.95 (95% CI, 1.40–6.24) and the prediction interval was 0.40–21.53. The OR for NVO was 0.66 (95% CI, 0.04–12.03) and the prediction interval was 0–114.53. Conclusions. When all studies as well as when NVO studies only were evaluated, there was no significant difference in bacterial pathogen yield based on antibiotic exposure. When VO studies were evaluated separately, there were fewer pathogens recovered than when antibiotics were administered prior to obtaining bone cultures.