CONTEXT: Half of children experience wheezing by age 6 years, and optimal strategies for preventing severe exacerbations are not well defined. OBJECTIVE: Synthesize the evidence of the effects of daily inhaled corticosteroids (ICS), intermittent ICS, and montelukast in preventing severe exacerbations among preschool children with recurrent wheeze. DATA SOURCES: Medline (1946, 2/25/15), Embase (1947, 2/25/15), CENTRAL. STUDY SELECTION: Studies were included based on design (randomized controlled trials), population (children ≤6 years with asthma or recurrent wheeze), intervention and comparison (daily ICS vs placebo, intermittent ICS vs placebo, daily ICS vs intermittent ICS, ICS vs montelukast), and outcome (exacerbations necessitating systemic steroids). DATA EXTRACTION: Completed by 2 independent reviewers. RESULTS: Twenty-two studies (N = 4550) were included. Fifteen studies (N = 3278) compared daily ICS with placebo and showed reduced exacerbations with daily medium-dose ICS (risk ratio [RR] 0.70; 95% confidence interval [CI], 0.61-0.79; NNT = 9). Subgroup analysis of children with persistent asthma showed reduced exacerbations with daily ICS compared with placebo (8 studies, N = 2505; RR 0.56; 95% CI, 0.46-0.70; NNT = 11) and daily ICS compared with montelukast (1 study, N = 202; RR 0.59; 95% CI, 0.38-0.92). Subgroup analysis of children with intermittent asthma or viral-triggered wheezing showed reduced exacerbations with preemptive high-dose intermittent ICS compared with placebo (5 studies, N = 422; RR 0.65; 95% CI, 0.51-0.81; NNT = 6). LIMITATIONS: More studies are needed that directly compare these strategies. CONCLUSIONS: There is strong evidence to support daily ICS for preventing exacerbations in preschool children with recurrent wheeze, specifically in children with persistent asthma. For preschool children with intermittent asthma or viral-triggered wheezing, there is strong evidence to support intermittent ICS for preventing exacerbations.