Anti-tumor necrosis factor (TNF)-alpha agents promise better disease control for the treatment of ankylosing spondylitis resistant to classical disease-modifying treatments. Etanercept, a recombinant human TNF receptor fusion protein, is used to treat a variety of TNF-alpha-mediated diseases by inhibiting the biological activity of TNF-alpha. We experienced a case of pustular psoriasis in a 32-year-old man during anti-TNF-alpha therapy with etanercept. He had a history of ankylosing spondylitis for 2 years. Two years after treatment of etanercept, erythematous pustules developed on his palms and soles. He had no previous history of pustular psoriasis. The skin lesion improved as the etanercept therapy was stopped, but pustular skin eruption recurred as adalimumab, a different TNF-alpha inhibitor, was administered to manage his ankylosing spondylitis. Several TNF-alpha inhibitors have different molecular structures, but these inhibitors might have a similar potency to induce pustular psoriasis from this case.