Background and Objective: The promoter of the apolipoprotein E (APOE) gene is polymorphic at positions -491A/T, -427C/T and -219G/T. These single nucleotide polymorphisms may alter transcriptional activity and impact APOE expression due to differential binding of transcription factors. It has been suggested that the -491 A, -427 C and -219 T alleles are associated with a high risk of developing Alzheimer’s disease. This study aims to investigate the frequencies of APOE promoter polymorphisms in three major ethnic groups (Malay, Chinese and Indian) in Malaysia. Method: DNA was extracted from blood obtained from 290 healthy people (Malay: n= 92; Chinese: n= 105; and Indian: n= 93), and the promoter region was amplifi ed using PCR and genotyped by direct sequencing. Result: The Indian group has the lowest frequencies of - 491 A, - 427 C and - 219 T alleles (83.9%, 3.2% and 56.5%, respectively) compared to the Chinese group with the highest frequencies (97.1%, 11.9% and 67.1%, respectively). The frequencies in the Malay group were somewhere in between (94.6%, 8.2% and 61.4%, respectively). Moreover, for the - 491 and - 427 positions, the frequencies of possible genotypes viz., AA or AT or TT and CC or CT or TT, respectively, were statistically signifi cant (P < 0.05, Chi- Square Test) between the 3 ethnic groups. Conclusion: Based on the frequency of APOE promoter polymorphisms alone, the ethnic Indian may be predisposed to lower risks for AD than the Chinese or Malay.