The human leukocyte antigen (HLA)-B*2706 is a relatively rare subtype of HLA-B27. In contrast to most HLA-B27 subtypes, some studies have reported HLA-B*2706 to be protective against ankylosing spondylitis (AS). A systematic review and a meta-analysis of available studies was performed to investigate the association of HLA-B*2706 with AS. After literature review a random effect meta-analysis was performed. No studies were found comparing the frequency of HLA-B*2706 in AS patients and controls. Meta-analysis of seven studies using HLA-B27-positive AS patients and controls showed a protective effect of HLA-B*2706 on development of AS in HLA-B27 individuals (odds ratio = 0.128, 95% CI = 0.043–0.378, P < 0.001). The results of the meta-analysis of HLA-B*2706 in HLA-B27-positive patients and controls is preliminary evidence of a protective effect of HLA-B*2706 against AS in the population. There is a clear need for additional studies on HLA-B*2706 in AS. Due to the fact that HLA-B*2706 is more or less restricted to Southeast Asia, researchers in this part of the world may have an essential role in performing these studies.