Interannual variability of vegetation activity (i.e., photosynthesis) is strongly correlated with El Nino Southern Oscillation (ENSO). Globally, a reduction in carbon uptake by terrestrial ecosystems has been observed during the ENSO warm phase (El Nino) and the opposite during the cold phase (La Nina). However, this global perspective obscures the heterogeneous impacts of ENSO at regional scales. Particularly, ENSO has contrasting impacts on climate in northern South America (NSA) depending on the ENSO phase and geographical location, which in turn affect the activity of vegetation. Furthermore, changes of vegetation activity during multiple ENSO events are not well understood yet. In this study, we investigated the spatial and temporal differences in vegetation activity associated with ENSO variability and its three phases (El Nino, La Nina, Neutral) to identify hotspots of ENSO impacts in NSA, a region dominated by rainforest and savannas. To achieve this, we investigated time series of vegetation variables from 2001 to 2014 at moderate spatial resolution (0.0083 degrees). Data were aggregated through dimensionality reduction analysis (i.e., Global Principal Component Analysis). The leading principal component served as a proxy of vegetation activity (VAC). We calculated the cross-correlation between VAC and the multivariate ENSO index separately for each ENSO phase. Our results show that El Nino phase has a stronger impact on vegetation activity both in intensity and duration than La Nina phase. Moreover, seasonally dry ecoregions were more susceptible to El Nino impacts on vegetation activity. Understanding these differences is key for regional adaptation and differentiated management of ecosystems. Precipitation and temperature are important climatic drivers of vegetation processes. In particular, El Nino Southern Oscillation (ENSO) events are related to changes in precipitation and temperature over large regions, which in turn affects the activity of the vegetation. In northern South America (NSA), these changes on climate are opposite during the same ENSO event depending on the geographical location. Moreover, local conditions and vegetation type can moderate or amplified changes in vegetation activity. Currently, the contrasting vegetation changes during the ENSO warm (El Nino) and cold (La Nina) phase are not well understood in NSA. Furthermore, it is unknown where the largest vegetation variability is occurring during ENSO phases. We combined different vegetation variables related to vegetation greenness and plant productivity over 14 years to estimate changes in vegetation activity related to photosynthesis. In this way, we assessed the variability of vegetation activity during El Nino and La Nina. We found that variability of vegetation activity is stronger and longer during El Nino than La Nina. In addition, vegetation in semi-arid ecoregions was more susceptible to El Nino. A better understating of how vegetation activity varies during different ENSO phases will improve regional conservation strategies under the increasing ENSO frequencies. Interannual variability of vegetation activity in northern South America is related to changes in climate due to El Nino and La Nina eventsEl Nino events have a stronger impact on vegetation activity both in intensity and duration than La Nina eventsSemi-arid ecoregions are the most vulnerable to El Nino, but further investigation is required to understand underlying processes