There is still controversy on the management of septic arthritis in neonates. This study aims to investigate the treatment of septic arthritis in neonates.We reviewed 52 neonates (37 males and 15 females) with septic arthritis in our hospital during 2004 to 2015. The mean age at onset of infection was 17.5 ± 7.6 days, mean age at admission was 32.6 ± 10.7 days. A total of 56 joints were involved (22 knees, 18 shoulders, 13 hips, and 3 other joints). Thiryt-six patients underwent surgical drainage, 14 patients were treated nonoperatively, 2 families refused treatment. Forty-four patients (48 joints) were followed for 4.5 ± 1.2 years. Based on treatment, these 48 joints were divided into an operative group and a nonoperative group. Clinical presentations, imaging examination results, treatments, and outcomes were analyzed.Among the patients who were followed-up, the time from onset to treatment in the operatively managed group (12.7 ± 8.1 days) was significantly shorter than that in the conservatively managed group (20.0 ± 8.2 days). There were no significant differences between both groups on the age at onset, age at admission, imaging score, length of hospital stay, WBC counts, and intravenous medication time. Thirty-five sites (72.9%) recovered completely. There was no significant difference on recovery rate between operative and nonoperative group. Only 33.3% of the hips recovered, this was significantly lower than that of knee/ankle (85.0%) and shoulder/elbow (78.9%). Sequels were found in 13 joints. Logistic regression indicated that sex, imaging score, and hip joint involvement were predictors of sequel. One point of imaging score increased the risk of sequels by a factor of 2.960, and hip joint involvement increased the risk of sequels by a factor of 12.712. Females were more likely to have sequels than males.Surgical drainage is recommended for early diagnosed neonatal septic arthritis and hip infections. A conservative approach may be more efficient for patients whose diagnosis and treatment had been delayed for more than 2 weeks. Antibiotics should be administered intravenously for 2 weeks and then orally for another 2 weeks. First-generation cephalosporin and clindamycin are recommended empirical antibiotics before causative agent and its resistance pattern are known.