Background/Objectives: Praziquantel is a cornerstone of schistosomiasis control and elimination efforts. Continued surveillance of praziquantel efficacy is needed to monitor for the development of resistance, as well as to help public health officials gauge the effect of mass praziquantel administration on schistosomiasis control in communities, since it is the only drug used in schistosomiasis control programs. The objective of this study was to assess the praziquantel cure rate and egg reduction rate against urogenital schistosomiasis. Methods: This study enrolled 977 children from 12 villages in Afar and Gambella, Ethiopia, who provided urine samples that were checked for Schistosoma haematobium infection at baseline using urine filtration microscopy. Infected individuals were provided a single dose of praziquantel (40 mg/kg body weight) and retested six weeks post-treatment. Results:S. haematobium was recovered from baseline urine specimens in 177 of 977 (18%) participating children. One hundred six of these children completed therapy and presented for subsequent evaluation at six weeks; 91 children were egg-free. The egg reduction rate was 97%; changes in egg burden among the 15 children who did not achieve cure varied widely. Cure rates were better among children with light-intensity infections. No significant differences in egg reduction rates were found based on the demographic variables examined. Conclusions: Standard praziquantel monotherapy remains an effective treatment against urogenital schistosomiasis in Ethiopia.