In November 2003, a large hepatitis A outbreak was identified among patrons of a single Pennsylvania restaurant. We investigated the cause of the outbreak and factors that contributed to its unprecedented size. Demographic and clinical outcome data were collected from patients with laboratory confirmation of hepatitis A, and restaurant workers were tested for hepatitis A. A case-control study was conducted among patrons who dined at the restaurant between October 3 and October 6, 2003. Sequence analysis was performed on a 315-nucleotide region of viral RNA extracted from serum specimens. Of 601 patients identified, 3 died; at least 124 were hospitalized. Of 425 patients who recalled a single dining date at the restaurant, 356 (84 percent) had dined there between October 3 and October 6. Among 240 patients in the case-control study, 218 had eaten mild salsa (91 percent), as compared with 45 of 130 controls (35 percent) (odds ratio, 19.6; 95 percent confidence interval, 11.0 to 34.9) for whom data were available. A total of 98 percent of patients and 58 percent of controls reported having eaten a menu item containing green onions (odds ratio, 33.3; 95 percent confidence interval, 12.8 to 86.2). All restaurant workers were tested, but none were identified who could have been the source of the outbreak. Sequences of hepatitis A virus from all 170 patients who were tested were identical. Mild salsa, which contained green onions grown in Mexico, was prepared in large batches at the restaurant and provided to all patrons. Green onions that were apparently contaminated before arrival at the restaurant caused this unusually large foodborne outbreak of hepatitis A. The inclusion of contaminated green onions in large batches that were served to all customers contributed to the size of the outbreak. Copyright 2005 Massachusetts Medical Society.