Although sunscreens are widely used to photoprotect patients with photosensitive lupus erythematosus (LE), standardized controlled studies that can prove their efficacy for this indication have been lacking. Therefore, in the present study, the capacity of three different, commercially available sunscreens to prevent the development of skin lesions that have been induced in LE patients under standardized, reproducible conditions by employing a provocative phototest was assessed. In a double blind, intraindividual comparative study, 11 patients with LE were photoprovoked according to a standard protocol. All patients developed LE-specific skin lesions upon photoprovocation with a combination of UVA plus UVB radiation. Each of the sunscreens tested prevented the development of skin lesions in this assay, but to various extents. Suncreen A (UVB: Octocrylene; UVA: Mexoryl SX, Mexoryl XL, Parsol 1789; TiO2) was by far the most effective by protecting in 11/11 patients. This protective capacity was corroborated by studies in which strong ICAM-1 mRNA expression was found in unprotected test areas, but not in sunscreen A pretreated sites. In contrast to sunscreen A, sunscreen B (UVB: Eusolex 6300, Parsol MCX, Uvinul T150, Neohelipan; UVA: Parsol 1789; TiO2) protected in 5 patients and sunscreen C (Eusolex 6300, Parsol MCX, Uvinul T150; UVA: Parsol 1789; TiO2) in 3 out of 11 patients. These studies indicate that the use of sunscreens is beneficial to LE patients because it can prevent the development of UV radiation-induced skin lesions. Effective protection, however, might vary considerably between different sunscreens.