Ceftriaxone in a dose of 250 mg given intramuscularly is currently recommended for the treatment of chancroid. Among 133 men in Nairobi, Kenya, with culture-proven chancroid, who were treated with ceftriaxone, treatment failed in 35%. Poor outcome was associated with human immunodeficiency virus type 1 seropositivity. Thus, treatment recommendations for chancroid should be reevaluated.