Background Intestinal parasitic infections are highly endemic among school-aged children in resource-limited settings. To lower their impact, preventive measures should be implemented that are sustainable with available resources. The aim of this study was to assess the impact of handwashing with soap and nail clipping on the prevention of intestinal parasite reinfections. Methods and Findings In this trial, 367 parasite-negative school-aged children (aged 6-15 y) were randomly assigned to receive both, one or the other, or neither of the interventions in a 2 x 2 factorial design. Assignment sequence was concealed. After 6 mo of follow-up, stool samples were examined using direct, concentration, and Kato-Katz methods. Hemoglobin levels were determined using a HemoCue spectrometer. The primary study outcomes were prevalence of intestinal parasite reinfection and infection intensity. The secondary outcome was anemia prevalence. Analysis was by intention to treat. Main effects were adjusted for sex, age, drinking water source, latrine use, pre-treatment parasites, handwashing with soap and nail clipping at baseline, and the other factor in the additive model. Fourteen percent (95% CI: 9% to 19%) of the children in the handwashing with soap intervention group were reinfected versus 29% (95% CI: 22% to 36%) in the groups with no handwashing with soap (adjusted odds ratio [AOR] 0.32, 95% CI: 0.17 to 0.62). Similarly, 17% (95% CI: 12% to 22%) of the children in the nail clipping intervention group were reinfected versus 26% (95% CI: 20% to 32%) in the groups with no nail clipping (AOR 0.51, 95% CI: 0.27 to 0.95). Likewise, following the intervention, 13% (95% CI: 8% to 18%) of the children in the handwashing group were anemic versus 23% (95% CI: 17% to 29%) in the groups with no handwashing with soap (AOR 0.39, 95% CI: 0.20 to 0.78). The prevalence of anemia did not differ significantly between children in the nail clipping group and those in the groups with no nail clipping (AOR 0.53, 95% CI: 0.27 to 1.04). The intensive follow-up and monitoring during this study made it such that the assessment of the observed intervention benefits was under rather ideal circumstances, and hence the study could possibly overestimate the effects when compared to usual conditions. Conclusions Handwashing with soap at key times and weekly nail clipping significantly decreased intestinal parasite reinfection rates. Furthermore, the handwashing intervention significantly reduced anemia prevalence in children. The next essential step should be implementing pragmatic studies and developing more effective approaches to promote and implement handwashing with soap and nail clipping at larger scales.