During January-April 2002, Salmonella serotype Newport was isolated from 47 persons in five states: New York (34 cases), Michigan (five), Pennsylvania (four), Ohio (two), and Connecticut (two). Antimicrobial-susceptibility testing of three isolates by CDC revealed resistance to amoxicillin/clavulanate, ampicillin, cefoxitin, ceftiofur, cephalothin, chloramphenicol, streptomycin, sulfamethoxazole, and tetracycline. In addition, two of three isolates were resistant to kanamycin; two had decreased susceptibility or resistance to ceftriaxone. To determine the cause of the outbreak, the New York State Department of Health (NYSDOH) and CDC conducted a case-control study. This report summarizes the results of this investigation, which implicated exposure to raw or undercooked ground beef as the vehicle of transmission. The findings also highlight the emergence of multidrug-resistant S. Newport in the United States. These strains exhibit decreased susceptibility or resistance to ceftriaxone, thereby complicating empiric therapy for serious Salmonella infections. Clinicians should be informed of the emergence of these S. Newport strains, and persons should refrain from eating undercooked ground beef and wash their hands after handling raw ground beef.