OBJECTIVES: The safety of long-acting beta agonists (LABAs) has been in much debate in recent years, resulting from controversial findings reported by various clinical and observational studies with adults. Very limited data on LABA use are available for children and adolescents with asthma. The objective of this study is to assess the risk of severe asthma exacerbations (SAEs) associated with LABA use among children and adolescents. METHODS: The primary data source is the MarketScan Medicaid database from 2002 to 2007.  A total of 783,368 patients (ages 0-18) with asthma were selected and divided into two cohorts:  405,941 with newly-diagnosed asthma and 377,427 with pre-existing asthma.   Drug use was tracked of inhaled corticosteroids (ICSs), LABAs, ICS/LABA combination drugs, short-acting beta agonists (SABAs), leukotriene modifiers, and oral and IV steroids.  Cox proportional hazard regressions were estimated to assess the risk of SAEs associated with different drug regimens. RESULTS: Approximately 9.5% patients were hospitalized or received intubation, while 60.8% visited the emergency department (ED). Hazard ratios of ED visits for newly-diagnosed and pre-existing-asthma patients were as follows: 0.60 (0.53-0.69) and 0.68 (0.62-0.75) for patients on a LABA without ICS; 0.69 (0.67-0.72) and 0.77 (0.75-0.80) for those on a LABA/ICS single inhaler; and 1.43 (1.41-1.45) and 1.33 (1.31-1.34) for African Americans, respectively.  Hazard ratios for hospitalization or intubation for newly-diagnosed and pre-existing-asthma patients were as follows: 0.43 (95% CI 0.22-0.84) and 1.30 (0.96-1.76) for patients on a LABA without ICS; 1.19 (1.05-1.36) and 1.65 (1.45-1.89) for those on a LABA/ICS single inhaler.  Other key risk factors (p<0.0001) included an alcohol/substance abuse disorder, pregnancy, obesity, and upper respiratory tract infection. CONCLUSIONS: Relative to SABA-only therapy, LABA use is associated with a lower risk of ED visits. Certain patients with asthma, such as pregnant adolescents and African Americans, are particularly vulnerable to SAEs.