IntroductionThe uptake trend of a new vaccine is unpredictable and may reflect the quality of introduction process and community acceptance. The objective of this study was to conduct a trend analysis of RTS,S malaria vaccine uptake in the seven pilot regions of Ghana from 2019 to 2022. The findings are envisaged to strengthen malaria vaccine introductions in the future. MethodsA retrospective analysis was conducted on routine childhood immunisation data for 2019–2022. Coverages for the first (RTS,S1), second (RTS,S2), third (RTS,S3) and fourth (RTS,S4) doses of malaria vaccine; third dose of diphtheria, tetanus, pertussis-containing vaccine (DTP3/Penta3); first dose measles-rubella (MR1) and second dose measles-rubella (MR2) vaccines were calculated. Dropout rates and uptake gaps were estimated to assess variations in the uptake of consecutive RTS,S schedules; and the differences in the uptake of RTS,S and the comparator vaccines, respectively. ResultsNationally, the coverages of the first three doses of the RTS,S malaria vaccine rose sharply from 2019 (RTS,S1 = 54.9 %; RTS,S2 = 54.6 %; RTS,S3 = 38.6 %) through 2020 (RTS,S1 = 70.7 %; RTS,S2 = 67.4 %; RTS,S3 = 66.3 %) to peaks in 2021 (RTS,S1 = 76.0 %; RTS,S2 = 73.1 %; RTS,S3 = 74.2 %), and declined marginally in 2022 (RTS,S1 = 74.0 %; RTS,S2 = 69.9 %; RTS,S3 = 71.3 %). For the fourth dose, the low uptake in 2020 (7.5 %) was followed by a steep rise in 2021 (46.9 %) that continued, but at a reduced rate to 50.6% in 2022. The dropout rates and uptake gaps were initially high but declined consistently over the study period. Generally, the trends in vaccination coverages, and dropout rates and uptake gaps at the national level were reflected in the respective regions. ConclusionThe coverage of RTS,S malaria vaccine improved consistently over the study period despite the low uptake in the early phase of the pilot. While the decreasing dropout rates and uptake gaps may indicate improved community acceptance, strengthening immunisation service delivery is crucial in sustaining the observed trajectory.