Abstractobjective To assess the efficacy and side effects of praziquantel in the treatment for Schistosoma mansoni infection in school children in Senbete Town, northeastern Ethiopia.methods A single stool specimen was collected from 342 school children and examined for S. mansoni ova using Kato-Katz technique (single slide) and formol-ether concentration technique. Positive individuals were treated with a single oral dose of praziquantel at 40 mg/kg body weight. Egg reduction and cure rates were assessed 4 weeks post-treatment. Structured questionnaires were also used to collect pre-treatment and 24-h post-treatment signs and symptoms to assess side effects of the drug.results Praziquantel reduced the egg rate by 79.46% and achieved a cure rate of 82.89% 4 weeks post-treatment. 86.67% of the children presented at least one transient drug-related sign and symptom 24-h post-treatment.conclusion Praziquantel demonstrated sufficient efficacy against S. mansoni in Senbete Town, northeastern Ethiopia. Mild and transient signs and symptoms associated with therapy disappeared within 24 h without specific treatment.