Background: Temporomandibular joint disorders (TMD) are a group of disorders involving temporomandibular joint and related structures. Interleukine-1 receptor antagonist (IL-1Ra) is an important anti-inflammatory molecule that competes with other interleukin-1 molecules. This study was designed to investigate the possible association of the IL-1Ra VNTR variant with the risk of TMD in the Turkish population. Methods: Peripheral blood samples were collected from 100 patients with TMD (23 males, 77 females) and 110 healthy individuals (35 males, 75 females). Genotyping of IL-1Ra 86 bp VNTR variant was evaluated by gel electrophoresis after polymerase chain reaction (PCR). Results: Our results show that there is a statistically significant difference between TMD patients and control group with respect to IL-1Ra genotype distribution and allele frequencies. 1.2, 1.4, and 4.4 genotypes were more common in patients, while 2.2 and 3.3 genotypes were rarer (P<.000). Frequency of alleles 1 and 4 was higher in patient groups (P<.000), whereas alleles 2 and 3 had a lower frequency in patients with TMD (P<.000). Conclusions: This is the first correlation study that evaluates the association between IL-1Ra gene VNTR variant and TMD. The VNTR variant related to IL-1Ra gene showed a strong pattern of association with TMD that may have a potential impact on disease counseling and management. Larger studies with various ethnicities are needed to establish the impact of IL-1Ra VNTR variant on risk of developing TMD.