Abstract: Objective To determine the epidemiological and etiological characteristics of hand, foot and mouth disease (HFMD) in Yantai, Shandong province. Methods The data of cases of hand, foot and mouth disease were collected for the comparison of incidence rates, demographics and geographical distribution of the cases in 2007 and 2008. In 2008, a total of 79 stool samples were collected from hospitalized cases for etiological identification using RT-PCR and viral isolation. Results The incidence rate of HFMD (39.91/lakh) in 2008 was a sharp decrease of 25.55% since 2007 (53.80/lakh). Cases in the two years involved 93.92% and 95.27% villages and towns, respectively. Most cases of HFMD were located in south and north regions of Yantai in 2007, whereas in 2008, most cases were in the northeast. The incidence rate peaked in June, 2007 and May, 2008. RT-PCR revealed 74.65% EV71-positive and 29.58% CA16-positive samples, and cell culture suggested 63.51% and 40.54%, respectively. Conclusion Despite reduction in the overall incidence, the disease involved a larger area in 2008. Following the prevalence, decline in the incidence rate was observed in the next year in highly prevalent areas in contrast to significant increase in that of peripheral areas which were less involved before. Summer and autumn were the seasonal peak of HFMD prevalence, which came one month earlier with milder peak value in 2008 than in 2007. EV71 was the dominant pathogenic strain of HFMD in Yantai in 2008.