Background. MS incidence has increased among females, suggesting the presence of environmental effect. Object. Regional differences and temporal changes in gender-specific MS incidence were studied in Finland. Methods. Cases from Jan 1, 1981 to Dec 31, 2010 in Pirkanmaa, Seinäjoki and Vaasa districts were included. The standardized incidence rates (SIR), incidences per 10(5) person years with 95% confidence intervals (CI), and female-to-male ratios (F/M) were determined by district. Results. 1617 cases were included. Compared to Pirkanmaa, the MS risk was 1.9-fold (95% CI: 1.7-2.0) greater in Seinäjoki and 1.2-fold (95% CI: 1.1-1.4) in Vaasa, and the risk was high for both genders. The incidence trend stabilized in Seinäjoki and Vaasa, accompanied by an increase in the F/M ratio. A steady increase in Pirkanmaa was accompanied by a high F/M ratio. Conclusion. A high female preponderance accompanied a general increase in incidence since the 1990s, suggesting the influence of environmental factors. In high-risk districts, increased MS risk prevailed in both genders. High risk reflects both genetic and environmental effects. These effects may be shared with autoimmune diseases such as type 1 diabetes mellitus; the incidence of which follows MS in Finland. Population-based case-control studies are needed to identify these factor effects.