BACKGROUND: In the Philippines, malaria morbidity and mortality have decreased since the 1990s by effective malaria control. Several epidemiological surveys have been performed in the country, but the characteristics of the Plasmodium falciparum populations are not yet fully understood. In this study, the genetic structure of P. falciparum populations in the Philippines was examined. METHODS: Population genetic analyses based on polymorphisms of 10 microsatellite loci of the parasite were conducted on 92 isolates from three provinces (Kalinga, Palawan, and Davao del Norte) with different malaria endemicity. RESULTS: The levels of genetic diversity and the effective population sizes of P. falciparum in the Philippines were similar to those reported in the mainland of Southeast Asia or South America. In the low malaria transmission area (Kalinga), there was a low level of genetic diversity and a strong linkage disequilibrium (LD) when the single-clone haplotype (SCH) was used in the multilocus LD analysis, while in the high malaria transmission areas (Palawan and Davao del Norte), there was a high level of genetic diversity and a weak LD when SCH was used in the multilocus LD analysis. On the other hand, when the unique haplotypes were used in the multilocus LD analysis, no significant LD was observed in the Kalinga and the Palawan populations. The Kalinga and the Palawan populations were, therefore, estimated to have an epidemic population structure. The three populations were moderately differentiated from each other. CONCLUSION: In each area, the level of genetic diversity correlates with the local malaria endemicity. These findings confirm that population genetic analyses using microsatellite loci are a useful tool for evaluating malaria endemicity.