To gain insight into the dynamics of intestinal Entamoeba histolytica infection, a longitudinal study was performed over an observation period of 15 months with a group of 383 randomly selected adult individuals (mean age, 38.5 years) living in an area of amebiasis endemicity in central Vietnam. Ameba infection was diagnosed by using species-specific PCR and DNA extracted directly from fecal samples. The results indicated an E. histolytica prevalence of 11.2% and an annual new infection rate of 4.1% in the study population. Follow-up of the 43 individuals who were E. histolytica positive at enrollment suggested a regular exponential decline in infection of about 3% per month and a mean half-life of infection of more than 15 months. However, the reinfection rate for this group of participants was 2.7 times higher than that predicted for the study population as a whole. Both the reappearance of the parasite after successful treatment of E. histolytica infection and changes in "genetic fingerprints" of parasites during the course of infection revealed an annual new infection rate of about 11.5%. Thus, the mean half-life of E. histolytica infection was calculated to be 12.9 months (95% confidence interval, 10.2 to 15.6 months). Notably, none of the participants developed symptoms compatible with invasive intestinal amebiasis, and only one of the subjects developed an amebic liver abscess during the observation period.