Introduction: Niger organized in 2013 a malaria chemoprevention campaign in children 3 to 59 months in some health districts (HD). The objective of the study is to assess the effectiveness of seasonal malaria chemoprevention (SCP) in children aged from 3 to 59 months in the health areas of Safo and Moullé in HD of Madarounfa in 2013. Methodology: An evaluative study in children aged 3-59 months was conducted. Data were collected using a questionnaire to health workers, an interview guide to community volunteers and mothers or children guardians. Our sample consisted of 141 mothers or children guardians, 12 community volunteers and 7 health workers serving in the Campaign sites of the health centers. Data were analyzed using the software STATA12. The chi-square test and p-value with 95% confidence intervals were used to search for a relationship between variables. Results: The coverage of the SCP was 86.6%. It was noted a decrease of 50% of clinical cases of malaria during the rainy season compared to the previous year at the same period in both health centers. Some minor side effects have been observed dominated by vomiting (54%). Conclusion: SCP remains a compelling strategy. Its implementation allows a significant reduction of malaria in the target.