The volume changes of 21 glaciers in the Cordillera Real have been determined between 1963 and 2006 using photogrammetric measurements. These data form the longest series of mass balances obtained with such accuracy in the tropical Andes. Our analysis reveals that temporal mass balance fluctuations are similar, revealing a common response to climate over the entire studied region. The mass of these glaciers has clearly been decreasing since 1975 without any significant acceleration of this trend over recent years. We have found a clear relationship between the average mass balance of these glaciers as a function of exposure and altitude. From this relationship, the ice volume loss of 376 glaciers has been assessed in this region. The results show that these glaciers lost 43% of their volume between 1963 and 2006, essentially over the 1975–2006 period and 48% of their surface area between 1975 and 2006.