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Background: H7N9 human cases were first detected in mainland China in March 2013. Circulation of this virus has continued each year shifting to typical winter months. We compared the clinical and epidemiologic characteristics for the first three waves of virus circulation. Methods: The first wave was defined as reported cases with onset dates between March 31-September 30, 2013, the second wave was defined as October 1, 2013-September 30, 2014 and the third wave was defined as October 1, 2014-September 30, 2015. We used simple descriptive statistics to compare characteristics of the three distinct waves of virus circulation. Results: In mainland China, 134 cases, 306 cases and 219 cases were detected and reported in first three waves, respectively. The median age of cases was statistically significantly older in the first wave (61 years vs. 56 years, 56 years, p < 0.001) compared to the following two waves. Most reported cases were among men in all three waves. There was no statistically significant difference between case fatality proportions (33, 42 and 45%, respectively, p = 0.08). There were no significant statistical differences for time from illness onset to first seeking healthcare, hospitalization, lab confirmation, initiation antiviral treatment and death between the three waves. A similar percentage of cases in all waves reported exposure to poultry or live poultry markets (87%, 88%, 90%, respectively). There was no statistically significant difference in the occurrence of severe disease between the each of the first three waves of virus circulation. Twenty-one clusters were reported during these three waves (4, 11 and 6 clusters, respectively), of which, 14 were considered to be possible human-to-human transmission. Conclusion: Though our case investigation for the first three waves found few differences between the epidemiologic and clinical characteristics, there is continued international concern about the pandemic potential of this virus. Since the virus continues to circulate, causes more severe disease, has the ability to mutate and become transmissible from human-to-human, and there is limited natural protection from infection in communities, it is critical that surveillance systems in China and elsewhere are alert to the influenza H7N9 virus. [ABSTRACT FROM AUTHOR]