OBJECTIVE To assess the safety and pharmacokinetics of high-dose magnesium sulfate (MgSO(4)) infusion in pediatric patients with status asthmaticus. METHODS A prospective cohort study within a 20-bed pediatric intensive care unit in an academic community hospital. Patients 2-18 years of age admitted with status asthmaticus between 10/2009 and 8/2010 were included in the study. All patients received standard therapy for asthma, while the treatment group received an intravenous magnesium sulfate bolus of 50-75 mg/kg (0.2-0.3 mmol/kg) followed by 40 mg/kg/h (0.16 mmol/kg/h) for 4 h. Patients were monitored for cardiorespiratory complications. The treatment group underwent four blood draws to assess pharmacokinetic parameters. RESULTS Nineteen patients were in the treatment group and 38 patients in the control group after exclusion criteria and consenting were completed. No clinically significant differences were found between groups. There were no interventions or discontinuations of MgSO(4) due to adverse events. In the treatment group, three patients had mild infusion-related reactions. Heart rate and respiratory rate were statistically significantly lower in the magnesium treatment group. CONCLUSIONS The continuous infusions of MgSO(4) were safe at the studied doses and maintained serum magnesium (SrMg) and ionized magnesium levels similar to levels required to produce smooth muscle relaxation in other clinical settings. Further studies are needed to investigate the efficacy of high-dose continuous MgSO(4) infusion as an adjunctive treatment for severe asthma treatment and determine the SrMg level required to maintain airway smooth muscle relaxation.