Several researchers have assessed the utility of Impulse Oscillometry System (IOS) in diagnosing and evaluating the severity of respiratory diseases in childhood, but none has investigated the impact of the fluctuations of IOS parameters in an individualized manner. In this two-year prospective study, we aimed to longitudinally evaluate changes in airflow limitation and bronchodilator responsiveness in steroid-naïve four- to six-year-old children during a virus-induced wheezing episode, with IOS pulmonary resistance parameters set at 5 (R5) and 20 (R20) Hz. Moreover, feasibility and reproducibility, in addition to the diagnostic properties of these parameters were examined. Lung function was assessed every six weeks (baseline), within the first 48 h following an acute wheezing episode (Day 0), after 10, and after 30 days. Forty-three out of 93 recruited children (4.5 ± 0.4 years old) experienced a wheezing episode during the study period. All children were able to perform the IOS effort in an acceptable and highly reproducible manner. R5 and R20 fluctuated independently of atopy, age, height, and weight. On Day 0, R5 values were significantly lower than the respective baseline values and returned to individual baseline levels within 10 days. Post-bronchodilation R5 values were similar to the baseline ones, reflecting a reversible airway obstruction on Day 0. Response to bronchodilation (ΔR5) was significantly more pronounced on Day 0. ΔR5 values lower than −20.5% had a sensitivity of 70% and a specificity of 76% and could accurately identify up to 75% of the examined preschoolers. This study provides evidence in favor of the objective utility of IOS as an easy, highly reproducible, and sensitive technique to assess clinically significant fluctuations and bronchodilation responses suggestive of airflow limitation. Reference values although necessary are suboptimal, utilizing the personal best values as personal reference is useful and reliable.