The Selva El Ocote Biosphere Reserve is located within the Mesoamerican biodiversity hotspot for global conservation. The area, poorly known relative to other humid tropical areas within Mexico, shows a mosaic of several types of forests, contains over 2000 species of vascular plants and 97 species of mammals, and plays a key role within Mexican tropical forests. We analyze the process of land-use/land-cover change (LUCC) within a 5755 km2 area which includes the reserve. Viability of conservation of the area was assessed by an integrated multi-temporal analysis of the LUCC process. Three cartographical data bases – from 1986, 1995 and 2000 – were used to assess rates and trends in LUCC for seven land cover types: agriculture/pasture (A/P); four types of second-growth forest (SGF); and two types of mature forest (tropical and temperate). Even when taking into account pathways of regeneration, results show a fast net loss of primary and secondary forests, primarily due to the establishment of A/P.For the entire area of study, the annual deforestation rate of tropical mature forests was 1.2% during the period 1986–1995, increasing to 6.8% for the period 1995–2000. For both periods, the annual deforestation rate was appreciably lower within the reserve (0.21% and 2.54%) than outside it (2.15% and 12.4%). The annual rate of conversion of tropical SGF to A/P was 1% during the first period and increased sixfold for the second period. Three future scenarios on forest cover were constructed using a Markovian model and annualizing LUCC transition matrices. Results show that between 29% and 86% of remaining forest may be lost within the next 23 years. Urgent action is necessary to reduce loss of biodiversity within this region. Particular attention must be paid to tropical SGF, which are rapidly being deforested.