AbstractBackgroundCutaneous lupus erythematosus is an umbrella term for a group of autoimmune connective tissue disorders affecting the skin. Discoid lupus erythematosus (DLE) is the chronic condition and most common form of cutaneous lupus erythematosus.AimsCurrent therapies of DLE are challenging and not completely satisfactory, highly expensive, off‐label, or poorly available (like antimalarials due to COVID‐19 outbreaks). Nicotinamide, also called niacinamide, is a water‐soluble form of vitamin B3 (niacin). Its multiple effects let us think that nicotinamide could be a therapy for lupus‐associated skin lesions.MethodsWe performed a prospective randomized double‐blind clinical trial on 60 subjects diagnosed with Discoid lupus erythematosus using topical Nicotinamide 2% and 4% preparations in form of cream and gel on skin and scalp lesions. Control group was included using only cream/gel base as placebo control.ResultsObtained data showed that topical Nicotinamide can be used for the treatment of DLE as adjuvant to other treatment regimens with good cosmetic results and minimal side effects. Topical 4% Nicotinamide is superior to 2% preparation in response but associated with a higher incidence of irritation.ConclusionTopical Nicotinamide can be used for the treatment of DLE as an adjuvant to other treatment regimens with good cosmetic results and minimal side effects. Further trials with long‐term therapy, follow‐up period, and bigger sample sizes are required.