We evaluated the long-term impact of single-dose diethylcarbamazine plus albendazole combination therapy with that of diethylcarbamazine alone on the control of soil-transmitted helminths (STH) in 2 blocks (revenue units) of Villupuram district, south India, as part of an ongoing mass drug administration (MDA) campaign for the elimination of lymphatic filariasis in 2001. The prevalence and intensities of STHs were studied in 287 children, aged 9 and 10 years (136 in the combination therapy cohort and 151 in the diethylcarbamazine alone cohort), using the Kato-Katz technique to examine stool samples at 4 time-points (baseline, and 3 weeks, 6 months and 11 months after MDA). The combination therapy showed long-term efficacy against STHs and the magnitude of control remained at a moderate and significant level for 11 months after MDA compared with the moderate gains of diethylcarbamazine alone. Single-dose MDA with albendazole and diethylcarbamazine combination therapy may prove to be a good strategy in treating multiple parasitic infections in endemic communities.