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Background: Shiga toxin-producing Escherichia coli (STEC) are an important cause of diarrhea and the major cause of postdiarrheal hemolytic uremic syndrome. Non-O157 STEC infections are being recognized with greater frequency because of changing laboratory practices., Methods: Foodborne Diseases Active Surveillance Network (FoodNet) site staff conducted active, population-based surveillance for laboratory-confirmed STEC infections. We assessed frequency and incidence of STEC infections by serogroup and examined and compared demographic factors, clinical characteristics, and frequency of international travel among patients., Results: During 2000-2010, FoodNet sites reported 2006 cases of non-O157 STEC infection and 5688 cases of O157 STEC infections. The number of reported non-O157 STEC infections increased from an incidence of 0.12 per 100,000 population in 2000 to 0.95 per 100,000 in 2010; while the rate of O157 STEC infections decreased from 2.17 to 0.95 per 100,000. Among non-O157 STEC, six serogroups were most commonly reported: O26 (26%), O103 (22%), O111 (19%), O121 (6%), O45 (5%), and O145 (4%). Non-O157 STEC infections were more common among Hispanics, and infections were less severe than those caused by O157 STEC, but this varied by serogroup. Fewer non-O157 STEC infections were associated with outbreaks (7% versus 20% for O157), while more were associated with international travel (14% versus 3% for O157)., Conclusions: Improved understanding of the epidemiologic features of non-O157 STEC infections can inform food safety and other prevention efforts. To detect both O157 and non-O157 STEC infections, clinical laboratories should routinely and simultaneously test all stool specimens submitted for diagnosis of acute community-acquired diarrhea for O157 STEC and for Shiga toxin and ensure that isolates are sent to a public health laboratory for serotyping and subtyping.