Antibiotic treatment appears to shorten the duration of diarrhea and eradicate Vibrio cholerae. The objective of this study was to compare the efficacy of tetracycline with norfloxacin therapy in patients (adults and children) with acute severe watery diarrhea caused by VC 01 and VC 0139. Patients (adults and children) with acute severe watery diarrhea admitted to Bamrasnaradura Infectious Disease Hospital, Thailand were randomized to receive either tetracycline (500 mg qid in adults and 12.5 mg/kg qid in children) or norfloxacin (400 mg bid in adults and 7.5 mg/kg bid in children) for 3 days each. The duration of diarrhea and the fecal shedding were comparable between two groups. Thirteen cases were treated with tetracycline and twelve cases with norfloxacin. The results showed the mean duration of diarrhea in tetracycline-treated and norfloxacin-treated groups were 1.31 and 1.25 days, respectively. The mean fecal shedding in tetracycline-treated and norfloxacin-treated group were 1.38 and 1.33 days, respectively. However, there were no statistically significant differences between two groups of both comparisons (p > 0.05). All isolates (VC 01 and VC 0139) in this study were susceptible to both antibiotics. Tetracycline therapy is as good as norfloxacin therapy for quick recovery and time for bacterial eradication in patients with acute severe watery diarrhea caused by Vibrio cholerae. Children aged less than 8 years should not use tetracycline therapy because of its toxic effects.