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Understanding the response of vegetation and ecosystem resilience to climate variability and drought conditions is essential for ecosystem planning and management. In this study, we assessed the vegetation changes and ecosystem resilience in the Horn of Africa (HOA) since 2000 and detected their drivers based mainly on analysis of the Moderate Resolution Imaging Spectroradiometer (MODIS) products. We found that the annual and seasonal trends of NDVI (Normalized Difference Vegetation Index) generally increased during the last two decades over the Horn of Africa particularly in western parts of Ethiopia and Kenya. The weakest annual and seasonal NDVI trends were observed over the grassland cover and tropical arid agroecological zones. The NDVI variation negatively correlated with Land Surface Temperature (LST) and positively correlated with precipitation at a significant level (p < 0.05) account for 683,197 km2 and 533,385 km2 area, respectively. The ecosystem Water Use Efficiency (eWUE) showed overall increasing trends with larger values for the grassland biome. The precipitation had the most significant effect on eWUE variation compared to LST and annual SPEI (Standardized Evapotranspiration Index). There were about 54.9% of HOA resilient to drought disturbance, whereas 32.6% was completely not-resilient. The ecosystems in the humid agroecological zones, the cropland, and wetland were slightly not-resilient to severe drought conditions in the region. This study provides useful information for policy makers regarding ecosystem and dryland management in the context of climate change at both national and regional levels. [ABSTRACT FROM AUTHOR]