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Ghana witnessed an outbreak of measles in 2022 following the COVID-19 pandemic, and Savannah Region was among the regions severely impacted. The objective of this study was to conduct trend analysis of measles case incidence and measles-rubella (MR) vaccination coverage in the Savannah Region to identify gaps and propose remedial actions to mitigate future outbreaks of vaccine preventable diseases (VPDs). Analysis of measles surveillance and measles-rubella vaccination data for 2018–2022 was conducted to assess relationship between immunization coverage and measles case incidence. Data were extracted from the District Health Information Management System (DHIMS) platform and loaded into Microsoft Excel 16.0 spreadsheet for analysis. Coverages for first (MR1) and second (MR2) doses of measles-rubella vaccination, dropout rates, and measles incidence (per 100,000) were calculated. The coverage trend for both vaccine doses followed similar trajectories, increasing from 2018 to a peak in 2019, and declining sequentially thereafter to the lowest (for the study period) in 2022. Generally, MR1/MR2 dropout rate was high across all districts during the entire study period. The regional incidence of confirmed measles rose sharply from less than 1/1,000,000 in 2018–2021 to 94 in 2022. Wide variations in vaccination coverage and dropout rates were observed among the districts. There was moderate to fairly strong negative correlation between MR vaccination coverage and measles case incidence. The MR vaccination coverage in the Savannah Region declined probably due to pre-existing weaknesses in the immunization programme accentuated by impact of the COVID-19 pandemic. The lowered population immunity likely contributed to occurrence of the measles outbreak in 2022. Pragmatic actions are needed to catch-up on missed children, restore coverage to pre-pandemic levels, and strengthen the immunization programme as part of global efforts towards achieving the Immunization Agenda 2030 (IA2030) trajectory. [ABSTRACT FROM AUTHOR]