BACKGROUND Treatment of chronic idiopathic urticaria (CIU) is challenging because of its unpredictable course and negative influence on the quality of life. New treatments are being developed, but antihistaminics remain the cornerstone of the therapeutic approach. Newer generation antihistaminics such as loratadine and levocetirizine have already proved to be safe and efficacious for CIU. OBJECTIVE To choose the better drug between loratadine and levocetirizine for CIU, by comparing their efficacy and safety. METHODS A randomized, open, outdoor-based clinical study was conducted on 60 patients of CIU, to compare the two drugs. After initial clinical assessment and baseline investigations, loratadine was prescribed to 30 patients and levocetirizine to another 30 patients for four weeks. At follow-up, the patients were re-evaluated and then compared using different statistical tools. RESULTS The comparative study showed that the changes in differential eosinophil count (P = 0.006) and absolute eosinophil count (P = 0.003) in the levocetirizine group was statistically significant. The results of the Total Symptom Score showed better symptomatic improvement of CIU with levocetirizine as compared to loratadine. The overall incidence of adverse drug reactions was also found to be less in the levocetirizine group. CONCLUSIONS An analysis of the results of all the parameters of safety and efficacy proves the superiority of levocetirizine over loratadine for CIU.