In Southern France, where most wildfires occur, the fire size has never exceeded 6744 ha since 1991, whereas mega-fires have burned huge areas in other Mediterranean countries such as Spain and Portugal. It was interesting to find out what main factors drove the ignition of the largest fires that had occurred in this region of France. The study was carried out using the forest fires database Prométhée that records all fires occurring in the 15 départements of Southern France since 1973. However, the records preceding 1997 are not reliable, only the 1997–2010 period was investigated. Less than 1% of the fires (N = 260) recorded during this period were equal or larger than 100 ha whereas 78% of the fires were smaller than 1 ha. However these large fires accounted for 78% of the burned area and 66% of these fires occurred during the summer (July–August). The number of large fires and the burned area per year and per département were calculated and the proportions of fires causes were determined. In each département, the impact of different explanatory variables (land-cover, topographic, climatic or socio-economic) on the number of large fires and on the size of the burned area was investigated using multivariate and regression analyses. Results showed that high shrubland and pasture covers, high population and minor road densities as well as dryness in fall to spring were positively linked to the number of large fires whereas high forest cover, ruggedness, wetness in fall to spring were negatively linked to this parameter. High wildland vegetation cover, especially shrubland, wetness in fall–winter, dryness in summer during a long period, high unemployment rate and tourism pressure were positively linked to the burned area whereas wetness in summer, high farmland and pasture covers and high population density were negatively linked to this parameter. However, only shrubland cover and ruggedness were significant descriptors of both fire occurrence and burned area. The départements the most affected by such fires were those situated in the eastern part of the region, on the Mediterranean coast and the main fire cause was arson