Introduction: In pediatric patients with asthma, measurements of forced expiratory volume in 1 s (FEV₁) may be normal or may not correlate with symptom severity. Forced expiratory flow at 25–75% of the vital capacity (FEF_25–75%) is a potentially more sensitive parameter for assessing peripheral airway function. This post hoc analysis compared FEF_25–75% with FEV₁ as an endpoint to assess bronchodilator responsiveness in children with asthma. Methods: Change from baseline in trough FEF_25–75% and trough FEV₁ following treatment with either tiotropium (5 µg or 2.5 µg) or placebo Respimat^® was analyzed in four phase III trials in children (aged 6–11 years) and adolescents (aged 12–17 years) with symptomatic moderate (VivaTinA-asthma^® and PensieTinA-asthma^®) and mild (CanoTinA-asthma^® and RubaTinA-asthma^®) asthma. Data from all treatment arms were pooled and correlations between FEF_25–75% and FEV₁ were calculated and analyzed. Results: A total of 1590 patients were included in the analysis. Tiotropium Respimat^® consistently improved FEF_25–75% and FEV₁ versus placebo, although in adolescents with severe asthma, the observed improvements were not statistically significant. Improvements in FEF_25–75% response with tiotropium versus placebo were largely more pronounced than improvements in FEV₁. Statistical assessment of the correlation of FEV₁ and FEF_25–75% showed moderate-to-high correlations (Pearson’s correlation coefficients 0.73–0.80). Conclusions: In pediatric patients, FEF_25–75% may be a more sensitive measure to detect treatment response, certainly to tiotropium, than FEV₁ and should be evaluated as an additional lung function measurement.