Background Urticaria and allergic dermatoses remains a great challenge to treating dermatologist. Histamine is the major mediator in such disorders. Antihistamines as levocetrizine, fexofenadine and desloratadine are often used to treat such conditions. Ability of antihistamines to suppress the allergic response helps to evaluate the efficacy of the medicine. Objective To compare the efficacy of levocetrizine versus fexofenadine versus desloratadine in suppressing histamine induced wheals in adults. Method One hundred and two healthy adult volunteers completed the study. Subjects were randomized into 3 groups using an envelope method. First group received fexofenadine (N=36), second group received levocetrizine (N =37), and third group received desloratadine (N=29). Pretesting was performed by skin prick test with histamine 1% (positive control) and normal saline (negative control). Wheal size was recorded before and after the treatment (at 0.5, 1, 2, 4 and 24 hours). Result At 30 minutes and 1 hour fexofenadine showed statistically significant wheal suppression than levocetrizine and desloratadine (p=0.0016). However by 2 and 4 hours all three antihistamines; fexofenadine, levocetirizine and desloratadine showed significant suppression of wheal. Whereas at 24 hours desloratadine showed greater wheal suppression than levocetrizine and fexofenadine (p= 0.014). Conclusion The results of the present study showed that fexofenadine presented early onset of action but longer suppression of wheal size was seen with desloratadine as compared to other antihistamines. These potentials could be employed in clinical aspects; depending upon the response needed.