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Campylobacter is a leading cause of traveler's diarrhea in Thailand. Since resistance to quinolones is high among Campylobacter isolates, empiric therapy with quinolones for traveler's diarrhea may be ineffective in this region. We conducted an observational study among 169 U.S. military personnel with acute diarrhea and compared their microbiologic findings to those of 77 asymptomatic personnel deployed to Thailand in May 1998. Of 146 pathogenic bacterial isolates, the most common were nontyphoidal Salmonella (n = 31), enterotoxigenic Escherichia coli (n = 24), and C. jejuni/coli (n = 23). Campylobacter was strongly associated with disease (odds ratio = 5.9; 95% confidence interval = 1.3-37.3), with a more severe clinical presentation, and with a reduced functional ability at presentation (P = 0.02). In vitro resistance to ciprofloxacin was observed in 96% of the Campylobacter isolates. Sub-optimal treatment response to ciprofloxacin was observed in 17% of the cases of Campylobacter infection versus 6% due to other causes. These results highlight the importance of Campylobacter as a cause of severe traveler's diarrhea in Thailand and illustrates the ongoing problem with antibiotic-resistant strains and associated treatment problems.