The safety and tolerability of asthma medications are still a concern to many asthma patients receiving long-term treatment. Therefore, more safety data from long-term, controlled trials are needed. The aim of this study was to evaluate the safety and tolerability of long-term treatment with once-daily budesonide in children aged 5-10 yrs with mild persistent asthma of recent onset in the inhaled Steroid Treatment As Regular Therapy in early asthma (START) study. Children aged 5-10 yrs with early asthma were randomized to double-blind treatment with budesonide 200 microg or placebo once daily via Turbuhaler in addition to usual asthma therapy, for 3 yrs. Adverse events were recorded from both spontaneous reports and responses to standard questions, and asthma-related events and asthma control were recorded between visits and subsequently graded by the blinded investigators. Of the study population of 1981 children (1004 budesonide and 977 usual care), 81% (812 of 1004) in the budesonide group and 82% (797 of 977) in the usual care group experienced a total of 6414 events listed by preferred term (3209 budesonide plus usual care and 3205 placebo plus usual care). The most commonly reported events included respiratory infection, pharyngitis, rhinitis, viral infection and bronchitis, and there were no clinically relevant differences in incidence between treatments. There were no reports of tuberculosis or aspergillosis, and no evidence of increased risk of systemic or ocular adverse events with budesonide relative to placebo. There were 106 serious adverse events in the budesonide group and 128 with usual care. The most frequent, aggravated asthma, was more common with usual care than with budesonide. There were no deaths among children participating in START. In conclusion, the addition of once-daily inhaled budesonide 200 microg via Turbuhaler to usual care is safe and well tolerated in children with recent-onset mild persistent asthma.