Acute diarrhea is the most common infectious disease worldwide and its causes vary from one region to another. We aimed to analyze the spectrum and epidemiological characteristics of pathogens from 22,386 outpatients with acute diarrhea on the basis of surveillance data from Shanghai, China, during 2006–2011. The following 8 pathogens were isolated and identified using standard methods: Salmonella, Shigella, Vibrio cholerae, V. parahaemolyticus, enteropathogenic Escherichia coli, enterotoxigenic E. coli, enteroinvasive E. coli, and enterohemorrhagic E. coli. In total, 2,234 strains of pathogens were obtained and the overall isolation rate of these 8 pathogens gradually decreased from 17.1% in 2006 to 7.4% in 2011. V. parahaemolyticus was the most frequently identified pathogen, followed by Shigella and Salmonella. The isolation rate of V. parahaemolyticus notably varied by season, whereas Salmonella and Shigella infections showed little seasonal variation. Age-related variation was also observed. V. parahaemolyticus infection occurred more often in patients aged 20–40 years. S. enterica serovar Enteritidis and S. flexneri were the most common serotypes of Salmonella and Shigella, respectively. The descending trend observed in the isolation rate of pathogens from the current surveillance suggests an urgent requirement or improvement.