Gene expression profiles were assessed in patients with relapsing-remitting multiple sclerosis (RRMS) to identify gender effects. Clear gender differences in time to second relapse and time to EDSS=6.0 progression in patients with late onset of the disease (>40years) were evident, and occurred more rapidly in female RRMS patients. Identified molecular biological mechanisms were related to increased immune activation associated with prominent inhibition of apoptosis that enhanced inflammatory processes and were more evident in female RRMS patients. Our findings open possibilities to explore gender-dependent immunomodulatory treatments that will be based on gene expression mechanisms that set the difference between male and female RRMS patients.