Background Post-inflammatory erythema (PIE) is a common sequalae of acne inflammation, persistent post acne erythema (PAE) is cosmetically unacceptable and sometimes its complete clearance could not be achieved. Oxymetazoline (OXZ) is a synthetic, direct-acting, sympathomimetic agonist that is highly selective for the 1α-adrenoceptor. It is a potent vasoconstrictor and well known for its ability to clinically ‘get the red out’. Aim The aim of this study was to evaluate the efficacy and safety of topical oxymetazoline (OXZ) 1.5% in treatment of post acne erythema (PAE) in a left to right face comparative study. Methods This study was conducted on 40 patients diagnosed with post acne erythema for at least 3 months, the left side of the face was treated with topical OXZ 1.5% in liposomal base and was compared to the right side to which topical lipogel was applied as a control. Results According to the investigator’s global assessment of photographs and the analysis of erythema with image analysis software, topical OXZ was significantly effective in diminishing PAE when compared to topical placebo lipogel Conclusion Topical OXZ is a safe and effective treatment for post-acne erythema.