Objective To identify patterns of hand, foot and mouth disease (HFMD) incidence in China during declining incidence periods of 2008, 2009, and 2010. Methods Reported HFMD cases over a period of 25 months were extracted from the National Disease Reporting System (NDRS) and analyzed. An interrupted time series (ITS) technique was used to detect changes in HFMD incidence rates in terms of level and slope between declining incidence periods of the three years. Results Over 3.58 million HFMD cases younger than 5 years were reported to the NDRS between May 1, 2008, and May 31, 2011. Males comprised 63.4% of the cases. ITS analyses demonstrated a significant increase in incidence rate level (P<0.0001) when comparing the current period with the previous period. There were significant changes in declining slopes when comparing 2010 to 2009, and 2010 to 2008 (all P<0.005), but not 2009 to 2008. Conclusion Incremental changes in incidence rate level during the declining incidence periods of 2009 and 2010 can potentially be attributed to a few factors. The more steeply declining slope in 2010 compared with previous years could be ascribed to the implementation of more effective interventions and preventive strategies in 2010. Further investigation is required to examine this possibility. Objective To identify patterns of hand, foot and mouth disease (HFMD) incidence in China during declining incidence periods of 2008, 2009, and 2010. Methods Reported HFMD cases over a period of 25 months were extracted from the National Disease Reporting System (NDRS) and analyzed. An interrupted time series (ITS) was used to detect changes in HFMD incidence rates in terms of level and slope between declining incidence periods of the three years. Results Over 3.58 million HFMD cases younger than 5 years were reported to the NDRS between May 1, 2008, and May 31, 2011. Males 63 63% of cases were analyzed as demonstrated a significant increase in incidence rate level (P <0.0001) when comparing the current period with the previous period. declining slopes when comparing 2010 to 2009, and 2010 to 2008 (all P <0.005), but not 2009 to 2008. Conclusion Incremental changes in incidence rate level during the declining incidence periods of 2009 and 2010 can potentially be attributed to a few factors. The more steeply declining slope in 2010 compared with previous years could be ascribed to the implementation of more effective interventions and preventive strategies in 2010. Further investigation is required to examine this possibility.