Killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) loci are both highly polymorphic. The aim of this study was to perform a KIR genotype analysis and examine, in concert with HLA-B27 genotypes, their influence on ankylosing spondylitis (AS) susceptibility in two Asian populations (one from China, 42 patients and 30 controls, and another from Thailand, 30 patients and 16 controls). In the Chinese population, we observed an increase of KIR3DS1, KIR2DS5, and KIR2DL5 gene frequencies in AS patients (p(c) < 0.005, p(c) < 0.001, and p(c) < 0.01, respectively). A similar increase was reported in the Thai population: KIR3DS1, KIR2DS5, and KIR2DL5 gene frequencies were higher in AS (p(c) < 0.05, p < 0.05, and p(c) < 0.05, respectively). Upon analyzing the KIR3DL1/3DS1 genotypes, we determined significant differences in both populations. The frequency of 3DL1/3DL1 was decreased in AS (p(c) < 0.005 and p(c) < 0.05 in the Chinese and Thai populations, respectively), whereas 3DL1/3DS1 demonstrated an increased frequency in AS (p(c) < 0.005 in the Chinese population and p(c) < 0.05 in the Thai population).