A prospective randomized, double-blind, placebo-controlled study was conducted to assess the efficacy and safety of nitazoxanide in the treatment of diarrhea caused by Giardia intestinalis or Entamoeba histolytica and/or E. dispar in 89 adults and adolescents, 22 of whom were diagnosed with G. intestinalis, 53 with E. histolytica and/or E. dispar, and 14 with both G. intestinalis and E. histolytica and/or E. dispar. The study medication was administered as 1 nitazoxanide 500-mg tablet or a matching placebo twice daily for 3 days. Thirty-eight (81%) of 47 patients in the nitazoxanide treatment group resolved diarrhea within 7 days (median, 3 days) after initiation of treatment, versus 17 (40%) of 42 in the placebo group (P=.0002). With its efficacy in treating a broad spectrum of enteric protozoan pathogens, nitazoxanide could play an important role in the management of diarrhea caused by enteric protozoa, reducing morbidity and costs associated with these diarrheal illnesses.