The prevalence of type 2 diabetes mellitus has reached epidemic proportions worldwide. Type 2 diabetes is a consequence of complex interactions among multiple genetic variants and environmental risk factors. Polymorphisms in various candidate genes confer susceptibility to diabetes. This study was undertaken to analyse a single nucleotide polymorphism Trp64Arg (C↔T) in the ADRB3 gene and elucidate its effects on type 2 diabetes and its associated risk factors. The study included 200 type 2 diabetes patients and 300 age and gender matched healthy controls belonging to the ethnic Kashmiri population. Polymerase chain reaction-restriction fragment length polymorphism technique was used for genotyping and the results were validated by direct sequencing assay. Genotypes for Trp64Arg polymorphism were in Hardy-Weinberg equilibrium (χ(2)=0.48, p=NS). Frequency of the Arg64 allele was 40% and 10.2% in cases and controls, respectively (p<0.05; odds ratio 5.89; 95% CI; 3.69-9.39). The Arg64 allele was directly related to higher body mass index, waist-to-hip ratio, dyslipidemia and uncontrolled disease status. The study signifies that the Arg64 allele of the ADRB3 gene is a genotypic risk factor and confers susceptibility to type 2 diabetes, whereas the homozygous Trp64 genotype exerted a protective effect in our population.