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More than 50% of the Mexican flora is represented by 11,001 species of endemic vascular plants. These high levels of endemisms should be a primal criterion for the recognition of areas for conservation. However, it is unknown whether the current network of protected areas guarantees the conservation of endemic vascular plant species. We focused in the Sierra Madre Oriental (SMOr), a mountain chain along Eastern Mexico that is recognized as one of the most important hotspots of vascular plant endemism in the country. At present, SMOr includes 73 protected areas, but their effectiveness for conservation of endemic species has not been evaluated. We aimed to calculate the number of endemic species that are currently considered in protection areas and propose the recognition of new areas that may include a greater endemic species diversity. Hotspots of endemism in SMOr were identified using herbaria information of 734 endemic species. The location of hotspots were identified from distribution patterns generated in the program MaxEnt. Also, Marxan program to reconstruct a map to propose new protected areas that include a greater number of endemic species. We observed that the richest hotspots are located in broken terrains with temperate or semi-arid climates, chalky soils, and a mixture of forests and scrublands featuring pines and oaks. When considering that at least 10% of the geographic distribution of each species should be conserved, the current protection areas include 66% of the endemic species, which might be an acceptable percentage, although it excludes an important number of potentially threatened species. Therefore, we propose the recognition of ten more areas that might be promising for the conservation of the remaining 34% of endemic plants in SMOr. This study demonstrates that current efforts for conservation in Mexico may be greatly improved when considering the hotspots of vascular plant endemisms.