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Complex Regional Pain Syndrome (CRPS) is clinically characterized by pain in combination with sensory, autonomic, and motor symptoms that may include weakness, tremor, myoclonus and dystonia of the affected limb(s). The syndrome is multifactorial in origin and mostly attributed to tissue injury. There is some evidence that the human leukocyte antigen (HLA) system plays a role in the pathophysiology of CRPS, but previous studies lacked power. Here we performed the most extensive study investigating the contribution of HLA alleles (i.e. HLA-A, HLA-B, HLA-DRB1, and HLA-DQB1) in 150 CRPS patients who also had fixed dystonia. HLA-B62 (OR = 2.05 [95% CI 1.41–2.99], P = 0.0005) and HLA-DQ8 (OR = 1.75 [95% CI 1.20–2.57], P = 0.005) were found significantly associated with CRPS and dystonia. The association remained significant after correction (HLA-B62 Pcorrected [Pc] = 0.02 and HLA-DQ8 Pc = 0.04). The involvement of HLA-B62 and HLA-DQ8 in CRPS with dystonia may indicate that these HLA loci are implicated in the susceptibility or expression of the disease.