INTRODUCTION: Erythema multiforme is a hypersensitivity reaction caused by various factors, such as viruses, chemicals, and drugs. Electronic cigarettes (e-cigarettes) or vape is a battery-powered nicotine delivery device that substitutes for traditional cigarettes. The chemical components of vaping, including propylene glycol and nicotine, can cause hypersensitivity reactions. OBJECTIVE: To report a case of oral erythema multiforme in an e-cigarettes user, treatment, and review the literature regarding the impact of these devices on oral health. CLINICAL CASE: A 22-year-old woman came to the Oral Medicine Department with complaints of stomatitis causing pain, eating, and drinking difficulty, which started with fever and pimple-like on the lips. She was an active vape user for one year. Extraoral examination revealed no lesions on other body parts. The serosanguinolent crusts on the lips, an erosive area on the labial commissures and tended to bleed. Intraoral examination revealed white ulcers with yellowish edges and irregular, varying sizes in several parts of the oral mucosa. The anti-HSV-1 IgG laboratory results showed non-reactive, leading to a diagnosis of oral erythema multiforme. Management of oral conditions using 0.9% NaCl compress, dexamethasone mouthwash, and hyaluronic acid, applying 2% miconazole cream on labial commissures and vaseline album cream on the dry lips, and stopping vaping. Oral condition improved in a week of therapy. CONCLUSION: Erythema multiforme restricted to the mouth is rare, especially associated with electronic cigarettes. Early identification of oral ulcerative disorders is crucial for accurate diagnosis and treatment, where clinicians should consider oral erythema multiforme as a possible diagnosis.