Background: Preventive chemotherapy interventions have been identified as key tools for malaria prevention and control. Seasonal malaria chemoprevention (SMC) and intermittent preventive treatment of infants (IPTi) represent the two major chemoprevention measures recommended by the WHO since 2012. A large number of publications of clinical trials have reported on the efficacy and safety profile of these interventions. However, little literature exists on end-user experience. The objective of this study was to provide insights on the perceptions and attitudes towards SMC and IPTi to identify drivers of and barriers to acceptance.Methods: a total of 179 in-depth qualitative interviews were conducted with community health workers (CHWs), health center managers, parents of children receiving chemoprevention, and national decision-makers across eight countries in sub-Saharan Africa. Questionnaires were adapted to the malaria chemoprevention intervention in place in each country. The transcribed verbatim responses were coded and analyzed using a thematic approach.Results: Study data indicate that SMC is largely well perceived and accepted by end-users, mainly due to its generally favorable efficacy and safety profile. Despite this largely positive perception, coverage remained below 100%, with health-center managers and CHWs who participated in our survey estimating, respectively, that 88% and 92% of eligible children received the first dose each month. The main causes mentioned for missing doses were children’s absenteeism, children being sick, parents’ reluctance, and lack of staff. Regarding IPTi, results from participants based in Sierra Leone showed that the intervention was generally well accepted and integrated into the Expanded Programme on Immunization (EPI) program. High infant mortality rate due to malaria and supportive efficacy data led Sierra Leone to implement IPTi, although these arguments were not sufficient for respondents from other countries. At the field level, parents and CHWs from Sierra Leone recognized the efficacy of the intervention in protecting their infants from malaria. The main challenges encountered were access to water, crushing the tablets, and high staff turnover.Conclusions: SMC and IPTi are perceived as valuable interventions. Our study identified the key elements that need to be considered to facilitate the expansion of these two interventions to different geographies or age groups.