OBJECTIVES: We used the World Health Organisation database (Vigibase) to evaluate the contribution of a global spontaneous adverse event (AE) database for an analysis of benefit-risk for Glatiramer acetate (GA) in multiple sclerosis. METHODS: Vigibase is a passive surveillance system that in 2011 contained over 6 million reports of spontaneous AEs suspected of being linked to health care products from regulatory authorities in nearly 90 countries. GA, interferon beta-1a, interferon beta-1b (interferons) and natalizumab and the reactions suspected of being associated with them were identified. Disproportionality analyses used the Multi-item Poisson Gamma Shrinker method with WHO-ART diagnosis at the preferred term level for all AEs and for the standard combination of all WHO ´critical terms´. Statistical significance for disproportionality was defined as an Empirical Bayesian Geometric Mean lower fifth percentile (EBGM05) >2.0. Comparisons were made between GA versus all other drugs and GA versus interferons and natalizumab. Sales data for GA were available to calculate reporting rates.    RESULTS: A total of 2,320 cases with 6,680 AEs with a suspected relationship with GA and 20,155 cases with 72,326 AEs for interferons and natalizumab were identified. Compared with all other drugs in Vigibase and with interferons and natalizumab, GA was associated with several statistically significant observations of disproportionate reporting. WHO ´critical terms´ combined were not higher for GA versus interferons and natalizumab (EBGM of 0.84 (90% credibility interval 0.79-0.90). The reporting rate of WHO ´critical terms´ for GA was 69 events/100,000 person-year.  CONCLUSIONS: In a risk-benefit analysis of GA based on traditional meta-analysis, the number of AEs in eligible controlled placebo/untreated and head-to-head studies were limited. In such a situation analysis of a global large spontaneous AEs database permitted the assessment of non-common and important risks. However, the biases inherent in these databases need to be addressed.