This is a report on population genetics of -344 T>C polymorphism in Amerindians for the first time. The aim was to establish the frequency of this polymorphism present in the 5’ promoter region of the CYP11B2 gene in Amerindian (Mayans, Mixtecos, and Teenek) and Mestizo populations from Mexico. It has been associated with an aldosterone increase and hypertension. Analyses were carried out by 5’ exonuclease TaqMan genotyping assays in a group of 608 unrelated individuals belonging to four different Mexican populations (301 Mexican Mestizos, 106 Mayans, 151 Mixtecos, and 50 Teenek). The frequencies in these populations were compared to those reported in other ethnic groups. Results showed significant highest frequencies of -344 T allele in Mexican populations (Mestizos and Amerindians) when compared to Europeans and Asians (p < 0.05). This confirms uniqueness of Amerindian genetic profile. In summary, the distribution of -344 T allele of the CYP11B2 -344 T>C polymorphism distinguishes the Mexican population form others, including Europeans and Asians. The knowledge of the distribution of this allele could be useful in Mexican Amerindians for hypertension prevention, epidemiology and anthropology.