Eight hundred forty Vibrio cholerae O1 and 171 O139 strains isolated from diarrhoea patients from 1995-2007 in Orissa, India were analyzed to determine the changing trends of fluoroquinolone susceptibility pattern. Emergence of ciprofloxacin, 17.4% and norfloxacin, 13% resistant V. cholerae O1 was found in 1995 and peaked to 64. 8% and 63.2% respectively in the year 2007. Similarly emergence of ciprofloxacin, 13.7% and norfloxacin, 10.3% resistant V. cholerae O139 was found in 1995 and both peaked to 62.2% in the year 2001. Nalidixic acid resistant V. cholerae O1 was observed throughout the study period where as the emergence of nalidixic acid resistant V. cholerae O139 was found for the first time in 1999. Selective pressure exerted by nalidixic acid and disproportionate use of fluoroquinolones may be the predeterminant of the genesis of fluoroquinolone resistant V. cholerae O1 and O139 serogroup which must be closely monitored.