Background: Wheezing in early childhood has implications for respiratory morbidity in later life. Objectives: We evaluated respiratory health-related quality of life (HRQoL) in young adults ages 17-20 years with a history of early childhood wheezing. Methods: Between 1992 and 1993, 100 children ages < 24 months were treated in the hospital for a lower respiratory tract infection with wheezing, and we followed up this cohort. In 2010, 49 of the patients (cases) and 60 population-based controls attended a clinical follow-up. St. George's Respiratory Questionnaire (SGRQ) was used to evaluate respiratory HRQoL, expressed as symptom, activity, impact, and total scores. Results: The median (interquartile range) SGRQ symptom scores were higher (13.7 [3.8-29.1]) in the 49 subjects (cases) with early childhood wheezing compared with the 60 population controls (7.8 [0.0-18.3]; p = 0.019). However, there were no between-group differences in total scores or in other SGRQ domains. Current asthma was a major risk factor for reduced HRQoL. In univariate analyses, the median symptom scores were 20.2 in those with asthma and 7.8 in those without asthma (p < 0.001), and, in multivariate analyses, the odds ratio (OR) was 8.7 for high total scores (95% confidence intervals, 2.1-36.6). Other factors associated with reduced HRQoL were current allergy (OR 4.4 for symptom scores), overweight (OR 3.3 for activity scores), tobacco smoking (OR 4.3 for symptom scores), and female sex (OR 3.2 for impact score). Furthermore, we performed post hoc analyses by excluding those with asthma and those who smoked, and found no significant differences on SGRQ scores between the subjects (cases) and the controls. Conclusion: Hospitalization for wheezing in early childhood mainly had indirect effects on HRQoL by increasing the risk of asthma.