To assess the yield and clinical impact of image-guided bone biopsy for osteomyelitis of the appendicular skeleton. A literature search of several databases was conducted from inception to August 2023. Eligible studies reported patients who underwent image-guided bone biopsy for investigation of osteomyelitis of the appendicular skeleton. The pooled proportions were analyzed using a random-effects model. This review was registered in PROSPERO (CRD42023466419). From 370 initial studies screened, eight met the eligibility criteria, with a total of 700 patients. The pooled technical success rate was 99.6% (95% CI: 0.992, 1.001; I2 = 0%). Positive bone cultures were pooled at 31.9% (95% CI: 0.222, 0.416; I2 = 87.83%) and negative cultures at 68.1% (95% CI: 0.584, 0.778; I2 = 87.83%). Methicillin-Sensitive Staphylococcus Aureus and Methicillin-Resistant Staphylococcus Aureus yield was 24.5% (95% CI: 0.096, 0.394; I2 = 90.98%) and 7.6% (95% CI: 0.031, 0.121; I2 = 34.42%) respectively. Group A Streptococcus yield was 7.0% (95% CI: 0.014, 0.127; I2 = 70.94%). Polymicrobial culture yield was 15.7% (95% CI: 0.018, 0.297; I2 = 88.90%). Post-procedural management change rate was 36.5% (95% CI: 0.225, 0.504; I2 = 92.39%). No complications were reported across studies. For patients under investigation of osteomyelitis of the appendicular skeleton, image-guided bone biopsy demonstrates a good rate of technical success. Additional studies may provide further support for the use of image-guided bone biopsy in this population. Image-guided bone biopsy results lead to change in antibiotics therapy in a portion of patients with suspected osteomyelitis suggesting its potential utility in select patients.