Examination of stool specimens by Kato-Katz (K-K) thick smears is the standard method recommended by the WHO for field diagnosis of intestinal schistosomiasis. However, there is increasing concern that this technique has low diagnostic sensitivity. In 326 study subjects, we compared the diagnostic yield of examining one, three or five Kato-Katz thick smears prepared from one stool specimen using 41.7 mg templates. In a subset of 169 subjects who had no demonstrable Schistosoma mansoni eggs in their first three Kato-Katz thick smears, we assessed the comparative advantage of examining an additional three Kato-Katz thick smears from another stool specimen, taken four weeks later, to that of cumulative yield obtained by examining all five Kato-Katz thick smears derived from the first stool specimen. For all helminth infections, single Kato-Katz thick smear-based prevalence estimates were significantly lower than those obtained from triplet or quintet Kato-Katz thick smears. Prevalence of S. mansoni infection based on single, triplet and quintet Kato-Katz thick smears from one stool specimen were 31.3%, 45.7% and 52.1%, respectively. Prevalence estimate of S. mansoni based on quintet Kato-Katz thick smears from the first day stool specimens was not different from cumulative estimate obtained with two triplet Kato-Katz thick smears from two stool specimens, 52.1% and 52.8%, respectively. In conclusion, either examination of quintet Kato-Katz thick smears from one stool specimen using 41.7 mg template or initial triplet Kato-Katz thick smears from one stool specimen, and if these are negative, followed by examination of additional triplet Kato-Katz thick smears from subsequent day stool specimen can adequately assess individuals for infection status with S. mansoni.