Objective: To test the efficacy of a new topical vehicle formulation containing cetirizine in emu oil in treating inflammatory skin conditions. Methods: A single blind half body comparative study of patients with psoriasis, atopic and stasis dermatitis were all treated with midpotency topical steroid (desoximethasone) in propylene glycol base, desoximethasone and cetirizine in propylene glycol base, desoximethasone in emu oil base and desoximethasone with cetirizine dissolved in emu oil. Results: Based on patients’ ranking of creams’ efficacy, and supported by photographic data and investigators’ clinical assessment, results clearly indicated that desoximethasone and cetirizine in emu base was statistically more efficacious than either desoximethasone alone or with cetirizine in neutral propylene glycol base or desoximethasone in emu oil base (without cetirizine). Conclusions: Cetirizine and emu oil, having inherent anti-inflammatory and other beneficial properties synergistically, and by different biochemical pathways, enhance and magnify each other’s pharmaceutical effects that are useful in treatment of skin inflammatory diseases.