Objective To compare the costs of Danmu extract syrup and Xiaoer Chiqiao Qingre granules for the treatment of acute upper respiratory tract infection (AURI) in children. Methods We conducted this prospective cohort study from July 2018 to June 2020. Children with AURI in the pediatric outpatient department and emergency department of West China Second Hospital were enrolled, and were divided into two groups: Danmu extract syrup group (Danmu group) and Xiaoer Chiqiao Qingre granule group (Chiqiao group) according to the treatment. The pharmacoeconomic evaluation took the medical and health system as the research perspective and considered direct medical costs, including registration fees, drug fees, inspection fees, testing fees, and treatment fees. A cost-effectiveness analysis or a cost minimization analysis was adopted according to the results of efficacy between the two groups. Results We enrolled 1 036 children with AURI. After propensity score matching, 252 in the Danmu group and 253 in the Chiqiao group were included. There was no statistically significant difference in the symptom recovery time between the two groups. The cost minimization analysis showed that the total costs (median difference ?21.55) and drug costs (median difference ?7.24) of the Danmu group were significantly lower than those of the Chiqiao group (P<0.001). The results of the subgroup and sensitivity analyses were consistent with the primary analysis. Conclusion Danmu extract syrup is a cost-saving alternative compared with Chiqiao granules for AURI in children.