Whether maintenance antifungal prophylaxis against histoplasmosis should be continued life-long in patients with immune restoration after highly active antiretroviral therapy (HAART) remains unclear. We report a case of disseminated histoplasmosis involving the skin, lung, gastrointestinal tract, mesentery, and retroperitoneum in a 33-year-old man with acquired immunodeficiency syndrome. His symptoms improved after use of amphotericin B and itraconazole in addition to ileostomy to relieve the intestinal obstruction. After the start of HAART, he was able to discontinue itraconazole as maintenance therapy without relapse for 24 months.