A growing body of evidence supports the association between Stressful Life Events (SLEs) and increased risk for relapse in Multiple Sclerosis (MS). In this open-label, randomized, controlled, one-year prospective study we investigated the effects of escitalopram on stress-related relapses in 48 women with relapsing-remitting MS. Patients were randomly assigned either to receive escitalopram 10mg/day (e-group, N=24) or to continue with treatment as usual, as a control group (c-group, N=24). SLEs were documented weekly in self-report diaries and were classified afterwards as short- or long-term depending on their psychological impact as this was subjectively felt by the patient. The cumulative risk for relapse was 2.9 times higher for controls than for escitalopram-treated patients (95% CI=1.7-5.1, p<0.001) and it was influenced only by long-term SLEs. In the e-group only 3 or more long-term SLEs were associated with a significant increase of the risk of a relapse during the following 4 weeks, and this risk was 4 times lower compared to the c-group. Our study shows preliminary evidence that escitalopram may constitute an effective and well-tolerated treatment option for the prevention of stress-related relapses in women with MS.