Background: Persistent cough in children often causes discomfort to children and parents reducing their quality of life. In spite of the extensive utilization of over the counter remedies against cough, for most of them efficacy in children has not been demonstrated. Methods: We conducted a randomized, double blind, placebo-controlled clinical trial recruiting 106 children with persistent cough to evaluate the efficacy and safety of KalobaTUSS®, a pediatric cough syrup based on acacia honey and on moieties derived from Malva sylvestris extract, Inula helenium, Plantago major extract, Helichrysum stoechas. Results: Children were orally treated with KalobaTUSS® or placebo for eight days. Children receiving KalobaTUSS® showed an early significant reduction in night-time and day-time cough score measured through a specific scale and a shorter duration of cough in comparison to placebo. Conclusions: Results show that KalobaTUSS® is well tolerated and produces positive effects by reducing severity and shortening the duration of cough in children. (Clinicaltrials.gov n. NCT04073251).