Research Article published by BioMed Research InternationalAdministeringmore than one treatmentmay increase Praziquantel cure and egg reduction rates, thereby hastening achievement of schistosomiasis transmission control. A total of 431 S. mansoni-infected schoolchildren were randomized to receive either a single or repeated 40mg/kg Praziquantel dose. Heights, weights, and haemoglobin levels were determined using a stadiometer, weighing scale, and HemoCue, respectively. At 8 weeks, cure rate was higher on repeated dose (93.10%) compared to single dose (68.68%) (𝑝 < 0.001).Theegg reduction rate was higher on repeated dose (97.54%) compared to single dose (87.27%) (𝑝 = 0.0062).Geometric mean egg intensity was lower among those on repeated dose (1.30 epg) compared to single dose (3.18 epg) (𝑝 = 0.036) but not at 5 (𝑝 > 0.05) and 8 (𝑝 > 0.05) months with no difference in reinfection rate. No difference in the prevalence of stunting was observed between the two treatment regimens (𝑝 > 0.05) at 8 months, but there was an increase in the prevalence of wasting among those on repeated dose (𝑝 < 0.001). There was an increase in the mean haemoglobin levels at 8 months with no difference between the two arms (𝑝 > 0.05). To achieve reduction of transmission intensity and disease control in highly endemic areas, repeated treatments alone may not be sufficient.This trial was registered with PACTR201601001416338.