Clobetasol propionate is known to be a very effective treatment for psoriasis; however, its use is limited by potent corticosteroid class related side effects such as hypothalamic-pituitary-adrenal (HPA) axis suppression and atrophogenicity. The aim of this single-center, parallel group, randomized study was to assess the HPA axis suppression potential, atrophogenicity, and ocular tolerability of clobetasol propionate shampoo in 26 patients with scalp psoriasis. Suitable subjects were treated once daily for 4 weeks with clobetasol propionate shampoo, to be rinsed off after 15 minutes or with a leave-on clobetasol propionate gel. The study demonstrated that clobetasol propionate shampoo did not lead to HPA axis suppression or to skin atrophy. Conversely, the gel led to HPA axis suppression and a decrease in skin thickness. Neither formulation had an impact on ocular safety. Despite the short contact application time, the clobetasol propionate shampoo provides similar efficacy results to the gel.