Studies in multiple sclerosis (MS) suggest a trend of increasing disease prevalence and incidence, and especially, a disproportional increase in the incidence of multiple sclerosis in women. The objective of this study was to evaluate the incidence of MS over 22 years and to determine the ratio in incidence of men to women in a health maintenance organization from Buenos Aires, Argentina. The population was made up of all members of a hospital-based HMO affiliated between January 1992 and December 2013. Each person was followed contributing time at risk. Cases with definite diagnosis of MS were included. Incidence density was calculated with 95 % confidence intervals and compared between women and men. 165,456 subjects were followed for a total of 1,488,575 person-years, of whom 42 developed MS. Incidence density was 3/100,000 person-years (95 % CI 2.1-3.5/100,000 person-years). During this period (1992-2013), the incidence rate in women increased from 1/100,000 (95 % CI 0.8-1.6) to 4.9/100,000 (95 % CI 4.1-5.4) (p < 0.001), while in men the incidence ranged from 1.4/100,000 (95 % CI 1-1.7) to 1.8 (1.3-2.1) (p = 0.16). Incidence density during the study period increased significantly in women but not in men. This is the first report of this phenomenon in Latin America region.