To assess the effectiveness of a 20-week, broad intervention to prevent reinfection by Ascaris lumbricoides (AL) and Giardia lamblia (GL) among indigenous schoolchildren in northern Mexico. A prospective, comparative, ecological study. Two isolated boarding schools, each hosting 100-120 children, 4-15 years of age, were selected based on physical infrastructure: intervention school (IS), modern; control school (CS), deprived. After initial diagnosis, children with positive stool samples received supervised treatment with oral nitazoxanide. Diagnoses were made with at least one positive microscopic result from two serial samples using the Faust technique, as reported by the independent observations of two trained, laboratory technicians. Post-treatment samples were taken, and only those with negative results were followed-up. The intervention included infrastructure improvements/maintenance and an educational preventive program for children, parents, and school personnel; no activities were undertaken in the CS. Baseline prevalence for AL was 37.5% at the IS versus 16.6% at the CS (P < 0.01); and for GL, 51.7% versus 37.8%, respectively. At the IS, 35.7% did not speak Spanish, compared to 6.7% in the CS (P < 0.01). Cure rates were similar in both schools for AL (~ 98%) and GL (~ 80%). Final prevalence and reinfection rates for GL were 10.4% versus 10.8%, and 17.2% versus 21% at the IS and CS, respectively. No children were infected/reinfected with AL in either school. Follow-up rates were 80%-83% at the CS and 90%-95% at the IS. Infection/reinfection rates were similar at the schools after 20 weeks. Supervised treatment alone every semester could effectively control AL/GL infections in this indigenous setting.