This study examines the genetic population structures of *Plasmodium falciparum* isolates from patients with either severe or uncomplicated malaria along the Thai-Myanmar border. Twelve microsatellite DNA loci were used to analyze 50 isolates (25 from severe malaria patients and 25 from uncomplicated malaria patients). The results showed that the genetic diversity and effective population sizes were greater in the uncomplicated malaria group compared to the severe malaria group. No evidence of genetic bottlenecks was observed in either group. Strong linkage disequilibrium was found in the uncomplicated malaria group. The two groups demonstrated significant genetic differentiation (P < 0.05), with allele frequencies for three of the 12 microsatellite loci differing significantly between them. These findings suggest that the genetic structure of *P. falciparum* populations in patients with severe malaria differs from that in patients with uncomplicated malaria, and that some of the studied loci may influence the clinical outcome of malaria.This study examines the genetic population structures of *Plasmodium falciparum* isolates from patients with either severe or uncomplicated malaria along the Thai-Myanmar border. Twelve microsatellite DNA loci were used to analyze 50 isolates (25 from severe malaria patients and 25 from uncomplicated malaria patients). The results showed that the genetic diversity and effective population sizes were greater in the uncomplicated malaria group compared to the severe malaria group. No evidence of genetic bottlenecks was observed in either group. Strong linkage disequilibrium was found in the uncomplicated malaria group. The two groups demonstrated significant genetic differentiation (P < 0.05), with allele frequencies for three of the 12 microsatellite loci differing significantly between them. These findings suggest that the genetic structure of *P. falciparum* populations in patients with severe malaria differs from that in patients with uncomplicated malaria, and that some of the studied loci may influence the clinical outcome of malaria.