OBJECTIVE Antihistamines are the first line of therapy for chronic idiopathic urticaria (CIU). The present study was designed considering the lack of reports comparing the efficacy and safety of commonly prescribed cetirizine and fexofenadine in the treatment of CIU. METHODS A total of 116 patients, aged 17 to 65 years, with CIU (urticarial wheals for at least two days per week for six consecutive weeks before entry) were enrolled in this randomised double-blind study. Study period was 28 days with patient visits on days 14 and 28 for investigator evaluation of the clinical response. Patient evaluation was on the basis of an analogue scale. Final response to treatment was judged as symptom free, partial improvement, and no improvement. RESULTS Ninety-seven patients (52 cetirizine, 45 fexofenadine) completed the study. The response to treatment in both the groups at the end of treatment period was as follows; symptom free [cetirizine 27(51.9%), fexofenadine 2(4.4%)], partial improvement [cetirizine 19(36.5%), fexofenadine 19(42.2%)], no improvement [cetirizine 6(11.5%), fexofenadine 24(53.3%)]. Side effects noted were mild with no significant difference between the two. CONCLUSIONS Cetirizine seems to have therapeutic advantage over fexofenadine in the treatment of CIU.