Background: Different regionalizations have been proposed for the Sierra Madre Oriental (SMOR), but none of them have analyzed its full floristic diversity. Hypothesis: The geographical distribution of the vascular plant species of the SMOR allows the identification of floristic regions with unique species that identify them as biogeographic units. Studied species: Vascular plants. Study site: Sierra Madre Oriental physiographic province, Mexico. Methods: Plant species distribution was analyzed in 1 × 1° latitude and longitude grid cells. Characteristic species (those with half or more of their known geographical distribution in Mexico in the SMOR) were identified, and a classification method was applied to distinguish biogeographic regions. Results: 8,472 species were recorded in the Sierra Madre Oriental, 3,433 of them considered characteristics, of which 2,158 are endemic to Mexico and 585 are considered strictly endemic to the province. The portions of the SMOR in the states of Coahuila, Nuevo León, Tamaulipas, and San Luis Potosí have a higher species richness and this richness decreases towards the south of the province. Five floristic districts were identified within the SMOR. Conclusions: The phytogeographic analysis carried out and its comparison with other regionalizations shows there is still disagreement in the biogeographic delimitation of the Sierra Madre Oriental and to achieve this goal it is necessary to include neighboring provinces in the analyzes, which will allow to identify their unique species and define their biogeographic limits in a more precise way.