Malaria is a leading cause of morbidity and mortality among children in Ghana. As part of the effort to inform local and national decision-making in preparation for possible malaria vaccine introduction, this qualitative study explored community-level factors that could affect vaccine acceptance in Ghana and provides recommendations for a health communications strategy. The study was conducted in two purposively selected districts: the Ashanti and Upper East Regions. A total of 25 focus group discussions, 107 in-depth interviews, and 21 semi-structured observations at Child Welfare Clinics were conducted. Malaria was acknowledged to be one of the most common health problems among children. While mosquitoes were linked to the cause and bed nets were considered to be the main preventive method, participants acknowledged that no single measure prevented malaria. The communities highly valued vaccines and cited vaccination as the main motivation for taking children to Child Welfare Clinics. Nevertheless, knowledge of specific vaccines and what they do was limited. While communities accepted the idea of minor vaccine side effects, other side effects perceived to be more serious could deter families from taking children for vaccination, especially during vaccination campaigns. Attendance at Child Welfare Clinics after age nine months was limited. Observations at clinics revealed that while two different opportunities for counseling were offered, little attention was given to addressing mothers’ specific concerns and to answering questions related to child immunization. Positive community attitudes toward vaccines and the understanding that malaria prevention requires a comprehensive approach would support the introduction of a malaria vaccine. These attitudes are bolstered by a well-established child welfare program and the availability in Ghana of active, flexible structures for conveying health information to communities. At the same time, it would be important to improve the quality of Child Welfare Clinic services, particularly in relation to communication around vaccination.