Introduction: Genes often have multiple polymorphisms that interact with each other and the environment in different individuals. Variability in the opioid receptors can influence opiate withdrawal and dependence. In humans, A118G Single Nucleotide Polymorphisms (SNP) on m-Opioid Receptor (MOR), 36 G>T in κ-Opioid Receptor (KOR), and T921C in the d-Opioid Receptor (DOR) have been found to associate with substance dependence.Methods: To investigate the association between opioid receptors gene polymorphism and heroin addiction, 100 control subjects with no history of opioid use, and 100 heroin addicts (50% males and 50% females) in Tehran (capital of Iran), were evaluated. A118G, 36 G>T, and T921C SNPs on the MOR, KOR, DOR genes, respectively, were genotyped by sequencing.Results: We found no differences in either allele or genotype frequency for MOR, KOR and DOR genes SNPs between controls and subjects addicted to heroin.Conclusion: The relationships among polymorphisms may be important in determining the risk profile for complex diseases such as addiction, but opioid addiction is a multifactorial syndrome which is partially hereditary and partially affected by the environment.