Background: Depression has been cited as a possible side effect of interferon beta-1b (IFNβ-1b) therapy in patients with MS. This association remains unproven because of a lack of longitudinal studies.Objective: To determine the changes in emotional state in relapsing-remitting (RR) MS patients during the first 2 years of treatment with IFNβ-1b.Methods: Emotional state was evaluated in a sample of 90 patients at the onset of IFNβ-1b treatment during an inclusion period of 2.5 years. Seventy-five patients were evaluated at their 12th month of treatment and 56 patients at their 24th month. We assessed their emotional state with the following psychological tests: Hamilton Depression Rating Scale, Beck Depression Inventory, and State-Trait Anxiety Inventory.Results: We found significant improvement in emotional state after the first and second years of treatment.Conclusions: Our findings show that IFNβ-1b does not increase depression or anxiety in RR MS patients during the first and second years of IFNβ-1b treatment. In fact, slight but significant improvement in depression and anxiety symptoms was observed during this period.