On June 6, 2007, a cluster of four human Salmonella serotype I 4,5,12:i:-* infections sharing a pulsed-field gel electrophoresis (PFGE) pattern was identified by the Pennsylvania Department of Health and reported to PulseNet. Initial investigations conducted during June--September 2007 by state and local health departments in collaboration with CDC did not identify a source of infection. This report summarizes the results of subsequent investigations of the outbreak, which determined that 401 cases of salmonellosis occurred in 41 states during 2007, with 32% of ill persons hospitalized. A multistate case-control study conducted during October 3-13 indicated that illness was associated with consumption of Banquet brand frozen, not-ready-to-eat pot pies (odds ratio = 23.6; p<0.001). Further investigation determined that 77% of patients who ate these pies cooked them in microwave ovens and that consumer confusion regarding microwaving instructions might have resulted in a failure to cook the product properly. A voluntary recall was issued by the manufacturer (ConAgra Foods Inc., Omaha, Nebraska) on October 11, 2007, for all nine brands of pot pies produced at the implicated plant (plant A). The outbreak strain was isolated from 13 samples of unopened Banquet pot pies collected from the homes of patients. This outbreak highlights the need to cook not-ready-to-eat frozen foods thoroughly; these products should be clearly labeled as requiring complete cooking, and cooking instructions should be validated to account for variability in microwave wattage and common misconceptions among consumers regarding the nature of not-ready-to-eat foods.