We evaluated the association between beta-adrenergic receptor genes (ADRB1 and ADRB2) polymorphism, cardiovascular risk, and acute coronary syndrome (ACS) in individuals from an Arab ethnicity. A total of 388 Qatari participants were assessed and genotyped for ADRB1 (rs1801252 & rs1801253) and ADRB2 (rs1042718 & rs1042713) polymorphisms using allele-specific PCR. Minor allele frequencies (MAF) in each single-nucleotide polymorphisms (SNPs) did not show statistically significant difference between cases and controls. A higher proportion of patients with ACS had homozygous minor alleles (GG) for rs1801253 (28.8% vs 17.1%; P = .019) compared with controls. Among cases with ACS, there was an association of minor allele frequency (G) for rs1801253 with severe coronary artery stenosis (0.485 vs 0.428; P = .04) than that of insignificant stenosis (<50% stenosis). There was a 3-fold increased risk of significant coronary stenosis in patients with diabetes mellitus (DM) and carrier of rs1801253 genotypes with dominant model (P = .01) and recessive model (P = .05). There is a possible synergic association between DM, carrier of ADRB1 (Arg389Gly) variants, and significant coronary artery stenosis among Arabs. Further prospective studies with larger sample sizes are warranted to support our findings.