Mu opioid receptor (OPRM1) gene variants, particularly the common A118G single nucleotide polymorphism (SNP), are among the most frequently studied candidate genes associated with opioid dependence. However, despite numerous case-control studies and metaanalyses, no defi nitive conclusion has been reached regarding the association of the A118G SNP and risk of developing opioid dependence. This study aimed to resolve this discrepancy by reinvestigating the association between A118G SNP allelic, and for the fi rst time, genotype frequencies and opioid dependence. A meta-analysis of sixteen case-control studies of opioid dependence was performed with a total of 5169 subjects. No association between the A118G allele (P = 0.23) and genotype (P = 0.34) frequencies and opioid dependence was found. However, signifi cant heterogeneity between studies precluded highly defi nitive conclusions. In addition, the possibility that other OPRM1 SNPs albeit rarer may infl uence the risk of opioid dependence remains to be investigated at this level. Nonetheless, despite no evidence of a direct association with risk of dependence, A118G may still infl uence the pharmacological response to opioids impacting on an individual's dosage requirements.