Previously published claims of large regional (northern vs southern states) differences in risks of fatality associated with tornadoes in the United States are reexamined. This new study extends earlier claims to include 1) data from a much longer time frame, 2) injuries as well as fatalities, and 3) more precise estimates of meteorological features of tornado events (specifically, a precise calculation of daytime vs nighttime and pathlength). The current study also includes formal mediation analyses involving variables that might explain regional differences. Results indicate that significant increases in the risk of fatality and injury do occur in southern states as compared with northern states. Mediation models show that these regional differences remain significant when meteorological factors of nocturnal occurrence and pathlength are included. Thus, these meteorological factors cannot explain regional differences in risk of fatality and injury, a failure that is unlikely to reflect a lack of data or a lack of precision in the measurement of potential mediators.