We conducted a randomized double-blinded study in Lima, Peru, to assess the tolerability andefficacy of a single 250-mg dose of ciprofloxacin in preventing diarrhea and Vibrio cholerae O1 infection among household contacts of bacteriologically confirmed index cases. Adult household contacts with negative baseline stool cultures were included. A total of 213 household contacts were evaluable.The study drugs were well tolerated in both groups. Ciprofloxacin did not prevent the acquisition of V. cholerae O1 infection nor the development of diarrhea. However, in a subgroup of 30 household contacts with positive baseline stool cultures a reduction in the bacterial load and a trend toward prevention of diarrhea were observed among ciprofloxacin recipients. When all household contacts were evaluated, a trend toward prevention of diarrhea was observed with the prophylactic regimen. Ciprofloxacinfailed to prevent V. cholerae O1 infections during a period of low transmissibility. © 1995 by The University of Chicago. All rights reserved.