Background Palmoplantar pustulosis (PPP) is characterized by sterile pustules with hyperkeratosis, erythema, scaling and fissuring on the palms and soles. PPP can present alone, or in association with palmoplantar pustular psoriasis (PPPP). Objectives To examine treatment with ustekinumab in patients with severe refractory PPPP. Methods Five patients (two men and three women, age 30-50 years) with severe refractory PPPP were treated with ustekinumab, according to a pre-established protocol. A 45 mg dose of ustekinumab was administered subcutaneously, followed by a 45 mg dose 4 weeks later and every 12 weeks thereafter. The severity of involvement and the therapeutic outcome were evaluated in every patient before, during and after treatment. Results Positive responses to ustekinumab were initially seen in all of the patients 2-3 weeks after the first dose, and were more remarkable after the second injection. Complete resolution of PPPP was achieved at week 20 and was maintained in all patients. Conclusions Ustekinumab appears to be an effective and safe therapeutic option in PPPP, leading to complete or nearly complete resolution of lesions and a significant improvement in patients' quality of life. © 2012 The Authors. BJD © 2012 British Association of Dermatologists.