Purpose <p>Inflammations of the upper respiratory tract (URT) are common both in adults and children and they are generally treated using aerosol therapy with mucolytic medications and steroids. When these inflammations affect children, the treatment must be rapid and resolutive to prevent complications. Steroids present some contraindications, i.e. alteration of smell, that must be considered especially in children. Therefore, alternative treatments that have similar efficacy but limited adverse effects should be considered. This study aims at evaluating the efficacy of Adelmidrol to treat inflammation of the URT in children.</p> Methods <p>Case-Control study. Control group used standard treatment for URT inflammation (mucolytics and steroids); treatment groups were treated by Adelmidrol spray. Sixty children (age range 2.5–4.5 years) were randomly assigned to (i) control group, (ii) treatment group 1 (TG1)- Adelmidrol nasal spray only and (iii) treatment group 2 (TG2), in which Adelmidrol was administered in both nasal and oral spray solution. The URT and the tympanic membrane were evaluated at T0, T1 (30 days) and T2 (90 days). The treatments were performed for 90 consecutive days.</p> Results <p>At the end of the treatment, TG2 (combination of nasal and oral sprays) had the best outcomes both on URT findings (χ²: <i>p</i> = 0.0004) and tympanic membrane conditions (χ²: <i>p</i> = 0.03). TG1 showed similar outcome of CG.</p> Conclusions <p>These preliminary results in our group of 60 children showed that Adelmidrol had the same efficacy of standard treatment when used as nasal spray only and was better than the standard treatment when used combining nasal and oral sprays. The molecule seems to offer the same benefit of standard treatment without side effects. If confirmed on a larger sample, the use of Adelmidrol could be suggested as an alternative to traditional treatment for the inflammation of URT in children.</p>