Objective To evaluate clinical efficacy and safety of loratadine combined with desloratadine in the treatment of chronic spontaneous urticaria(CSU)in children. Methods A total of 177 children with CSU were enrolled into this study, and randomly and equally divided into 3 groups:combination group treated with an age?based dose of desloratadine tablet every morning and a weight?based dose of loratadine tablet before sleep every night for consecutive 28 days, loratadine group treated with a half tablet of placebo(starch tablet)every morning and oral loratadine tablet before sleep every night for consecutive 28 days, and desloratadine group treated with a half tablet of placebo (starch tablet) every morning and oral desloratadine tablet before sleep every night for 28 consecutive days. Possible adverse reactions were observed and recorded after the start of treatment, and therapeutic effects were evaluated at the end of treatment. Results A total of 166 patients completed the trial, including 55 in the combination group, 56 in the loratadine group and 55 in the desloratadine group. After 28?day treatment, the total response rate was significantly higher in the combination group(90.9%, 50/55)than in the loratadine group (71.4%[40/56],χ2=6.865, P<0.05)and desloratadine group(74.5%[41/55],χ2=5.153, P<0.05). No significant difference in the incidence of adverse reactions was observed among the combination group (10.9%[6/55]), loratadine group (8.9%[5/56]) and desloratadine group (9.1%[5/55], P > 0.05). Conclusion Combination of loratadine and desloratadine was superior to loratadine or desloratadine alone in the treatment of childhood CSU, and there was no significant difference in the incidence of adverse reactions among the 3 treatment groups.