Although extremity chronic osteomyelitis is common in China, updated data were still limited regarding its characterizations. The present study aimed to review clinical features of extremity chronic osteomyelitis in Southern China.A retrospective analysis was conducted in the patients who had sought medical attention from January 2010 to April 2015 for extremity chronic osteomyelitis in Nanfang Hospital in Southern China. Clinical data were collected and analyzed.A total of 394 patients (307 males and 87 females) were included, giving a gender ratio of 3.53. The median age at first diagnosis was 42 years for all. The most frequent type was traumatic osteomyelitis (262 cases, 66.50%), which was mainly caused by open injury (166 cases, 63.36%) and during a road accident (91 cases, 34.73%). Single-site infection accounted for 81.98% (323 cases), with tibia (126 cases), femur (79 cases), calcaneus (37 cases), and toes (37 cases) as the top sites. The positive rate of intraoperative culture was 70.63% (214/303), 78.97% (169/214) of which was monomicrobial infection. Staphylococcus aureus (59 cases) was the most frequent bacteria for monomicrobial infection, followed by Pseudomonas aeruginosa (29 cases) and Escherichia coli (11 cases). The positive ratios of preoperative serum white blood cell (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) were 21.63%, 64.92%, 53.27%, 42.25%, 72.82%, and 66.67%, respectively. The most frequently used intravenous antibiotic was cephalosporins. The overall cure rate was 77.74%, with a total amputation rate of 16.75%.In this representative Chinese cohort, extremity chronic osteomyelitis was mostly caused by open injury and during a road accident, predominated in males and favored the tibia. S. aureus was the most frequent pathogenic organism. Preoperative elevated levels of serum IL-6, TNF-α, and ESR may be helpful diagnostic indicators of the disease. Most patients achieved a favorable clinical efficacy after appropriate treatment.