Introduction: Glatiramer acetate (GA) is a first-line therapy for the treatment of relapsing-remitting multiple sclerosis (RRMS). It has a well-characterized long-term safety profile and established efficacy, with over 2 million patient-years of exposure. Areas covered: To present long-term safety and tolerability findings for GA 20 mg/mL daily in the management of patients with multiple sclerosis (MS). A database analysis of all patients with MS who have ever been exposed to GA 20 mg/mL daily in clinical trials, including patients with up to 20 years of continuous treatment.Total exposure to GA in the clinical trials analyzed was 10,017 patient-years, and treatment duration ranged from 0 to 23.1 years (median 1.8 years). No unexpected adverse events (AEs) were recorded. The most common AEs were injection-site related (ISR), affecting 49% of patients receiving GA in clinical trials. Development of erythema at the injection site was the most common ISR, affecting 29.2% of study patients. Immediate post-injection reactions (IPIRs) were experienced by 24.0% of study patients; dyspnea was the most common IPIR, affecting 12.1% of patients. Expert opinion: The results of this analysis are consistent with long-term studies showing GA to be safe and generally well tolerated. © 2017 Informa UK Limited, trading as Taylor & Francis Group.