Background: There are conflicting data on the effect of day-care attendance and position in sibship on the development of wheezing. Objective: To investigate the relationship between day-care attendance and position in sibship with early childhood wheeze. Methods: Prospective population-based birth cohort. At age 5 years, we collected information on parentally reported symptoms (n = 922); lung function was ascertained using plethysmography (n = 745) and allergic sensitization by skin testing (n = 815). Participants were assigned into categories according to the age of entry to day-care (0-6, 6-12, >12 mo) and number of older siblings (0, 1, 2, >2). Results: Current wheeze was reported by 203 participants (22%); 224 (28%) were sensitized. In the multivariate model, sensitization (odds ratio, 2.47; 95% CI, 1.66-3.67), male sex (1.49, 1.01-2.20), maternal asthma (1.72, 1.10-2.68), and maternal smoking during pregnancy (2.15, 1.26-3.66) significantly increased the risk of wheezing. Entering day-care between 6 and 12 or after 12 months of age was significantly and inversely associated with current wheeze (0.25, 0.11-0.60; and 0.65, 0.44-0.98, respectively). Entry into nursery between 6 and 12 months reduced the risk of persistent wheezing (P = .04). We found no association between day-care attendance and lung function. Entering nursery in the first 6 months of life was associated with increased risk of atopy (2.47, 1.23-4.95). Having older siblings was associated only with rhinoconjunctivitis (0.72, 0.54-0.97). Conclusion: Day-care attendance was associated with a reduced risk of current wheezing in 5-year-old children. The protective effect appeared strongest for children who entered day-care between the ages of 6 and 12 months. © 2008 American Academy of Allergy, Asthma & Immunology.