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Background - Schistosomiasis is a water-based parasitic disease caused by blood flukes of the genus Schistosoma. Mass Drug Distribution (MDD) with Praziquantel is periodically recommended in schistosomiasis-endemic countries to prevent morbidity. In Mali, schistosomiasis still remains endemic, especially in Senegal and Niger rivers basin, although the strategy has been adopted since 2005. Our study aimed to assess the impact of annual school-based MDD. Materials and methods – The study was conducted at twelve sentinel sites across Kayes and Koulikoro regions. A cross-sectional study design was performed in April 2018 after four-or five-years post treatment with praziquantel (PZQ) depending on the statute of sites. At baseline (2014-2015) and for the control year (2018), 734 (386 boys and 347 girls) and 1708 (844 boys and 864 girls) school children of 7-14 years of age, were successfully examined respectively. Infections with Schistosoma haematobium and S. mansoni were diagnosed with the urine filtration and the Kato-Katz method respectively. Results – From eight schools treated in 2014, the four annual rounds of MDD with PZQ were associated with a significant decrease in S. haematobium prevalence in five sites (p<0,001) and a significant increase in one site (p<0,001). Of them, the prevalence of high-intensity (≥50 eggs/10mL of urine) significantly decreased in four previous sites but not in Diakalele where it increased ((p<0.001). In all the four sites treated in 2015, S. haematobium prevalence increased significantly in Kokoun and Samaya (P<0.05). The heavy infection increased slightly in Dougourakoro and Samaya (P>0.05). The prevalence of S. mansoni significantly decreased in three sites (p<0.001), increased in three and remains zero in the six others sites. Conclusion – Our findings show that five of the twelve sentinel sites have achieved the criterion of elimination of schistosomiasis due to Schistosoma haematobium as a major public health problem (Prevalence of heavy infection <1%); three have achieved the criterion of morbidity control (Prevalence of heavy infection <5%), whereas two sites remain confined below the control criterion. These results call for a strong improvement in the therapeutic coverage associating, education and provision of safe water, sanitation and hygiene to interrupt the transmission cycle of the schistosome.