This study aims to evaluate the factors influencing the adherence to the 2nd and 3rd doses during each cycle of seasonal malaria chemoprevention (SMC) in Burkina Faso, Mali, and Niger. Overall, 3,132 people were interviewed during surveys between 2019 and 2020 in 15 health districts. The median age was 30 years. In Burkina , Mali, and Niger, the proportions of non-adherence were 4.15% , 5.60%, and 13.30%, respectively (95% CI (-3.27% -0.37 %, p = 0.114 ) for the 2nd dose and 3.98%, 5.60% and 14.39% for the 3rd dose. The main cause of non-adherence to the 2nd and 3rd doses was other illnesses in 28.5% and 29.78% respectively in Burkina, 5.35% and 5.35% in Mali and 1.6% and 0.75% in Niger. It was followed by vomiting in 12.24% and 10.63% for Burkina and 2.45% and 3.78% in Niger. The last causes were refusal in 6.12% and 4.25% in Burkina , 33.9% and 15.25% in Mali and 0.8% and 1.51% in Niger. Non-adherence of doses related to parents was primary due to their absence in 28.5% and 27.65% in Burkina , 16.07% and 16.07% in Mali and 7.37 % and 6.06% in Niger. Travelling was the second cause in 12.24 % and 12.76% in Burkina , 19.64% and 19.64% in Mali and 0.81% and 0.75% in Niger. Non-adherence related to community distributors was mainly due to missing of the doses in 4.08% and 4.25% in Burkina , 23.21% and 23.21% in Mali, 77.04% and 76.51% in Niger. Our study reported very small proportions of non-adherence to 2nd and 3rd doses of SMC and identified the main causes of non-adherence.