High-elevation tropical mountain regions may be more strongly affected by future climate change than their surrounding lowlands. In the tropical Andes a significant increase in temperature and changes in precipitation patterns will likely affect size and distribution of glaciers and wetlands, ecosystem integrity, and water availability for human consumption, irrigation, and power production. However, detailed projections of future climate change in the tropical Andes are not yet available. Here we present first results for the end of the 21st century (2071–2100) using a regional climate model (RCM) based on two different emission scenarios (A2 and B2). The model adequately simulates the spatiotemporal variability of precipitation and temperature but displays a cool and wet bias, in particular along the eastern Andean slope during the wet season, December–February. Projections of changes in the 21st century indicate significant warming in the tropical Andes, which is enhanced at higher elevations and further amplified in the middle and upper troposphere. Temperature changes are spatially similar in both scenarios, but the amplitude is significantly higher in RCM-A2. The RCM-A2 scenario also shows a significant increase in interannual temperature variability, while it remains almost unchanged in RCM-B2 when compared to a 20th century control run. Changes in precipitation are spatially much less coherent, with both regions of increased and decreased precipitation across the Andes. These results provide a first attempt at quantifying future climate change in the tropical Andes and could serve as input for impact models to simulate anticipated changes in Andean glaciation, hydrology, and ecosystem integrity.