ObjectivesTo determine the influence of HLA-B27 positivity on risk of developing chronic nonbacterial osteomyelitis (CNO).MethodsHLA-B*27 genotype was assessed in 3 European CNO populations and compared with local control populations (572 cases, 33,256 controls). Regional or whole-body MRI was performed at diagnosis and follow-up in all cases which reduces the risk of disease misclassification. Genotyping was performed using either next generation DNA sequencing or PCR based molecular typing. Statistical analysis used Fisher’s exact test with Bonferroni correction and a fixed effects model for meta-analysis of odds ratios.ResultsHLA-B*27 frequency was higher in all 3 populations compared with local controls (combined odds ratio (OR) = 2.2,p-value = 3 × 10–11). This association was much stronger in male compared with female cases (OR = 1.99, correctedp-value = 0.015). However, the HLA-B*27 status was not statistically significantly associated with co-occurrence of psoriasis, arthritis or inflammatory bowel disease.ConclusionCarriage of HLA-B*27 is associated with greater risk of developing CNO, particularly in male cases.