There has been inadequate evaluation of an antibiotic for eradication of nontyphoidal salmonellae (NTS) in asymptomatic carriers. In a randomized, placebo-controlled trial, such efficacy was evaluated using 2 five-day regimens (norfloxacin, 400 mg twice per day, and azithromycin, 500 mg once per day) compared with placebo. The study included 265 food workers in an area of Thailand where NTS are endemic who were asymptomatic NTS carriers. The presence of NTS in stool samples was assessed on days 7, 30, 60, and 90 after start of treatment. At each assessment visit, <4% of participants in each of the 3 groups carried an initial Salmonella serotype; 16%-35% had new Salmonella serotypes detected, except on day 7 in the azithromycin group, when the rate was 4%. Sanitation was good at work but not at home. Selection of multidrug-resistant Salmonella enterica serotype Schwarzengrund was demonstrated. The study regimens were not better than placebo for treatment of asymptomatic food workers who carried NTS in an area where these organisms are endemic, and use of the regimens resulted in antimicrobial resistance.