Interventions such as antimalarial drugs, bed nets and insecticides have helped curb the burden of malaria in the past decade, yet malaria remains a leading cause of morbidity and mortality in children below the age of 5 years. In 2019, Ghana, Malawi and Kenya in sub-Saharan Africa (countries with moderate to high transmission areas of malaria and deaths) started piloting the RTS,S/AS01E malaria vaccine in selected regions. Using qualitative methods, this study examined the main factors (forces) that will influence or hinder the nationwide implementation of the malaria vaccine, if approved, in Ghana. We conducted in-depth interviews with 12 key individuals (national, research/academia and programme implementing partners) in the public health sector in Ghana from October 2018 to February 2019. Results were analysed using Kurt Lewin's force field analysis to understand how organizations interact with their external environment in the delivery of health policies such as the implementation of the malaria vaccine. We found that the disease burden of malaria deaths in Ghana, the efficacy of the vaccine, stakeholder involvement and evidence for the feasibility of vaccine delivery generated by the consortium of researchers (body of researchers) that can track the implementation were the driving forces to scale up the vaccine into a routine health system. On the other hand, the needed logistics, funding, administration of the four-dose vaccine and follow-up were identified as potential barriers. The most influential force collectively highlighted by the respondents was the disease burden, and the most influential barrier was the logistics of delivering the vaccine. Our findings provide decision makers with key barriers and facilitators to guide policy and decision-making for malaria control in Ghana and other similar settings in low- and middle-income countries.