Hand, foot, and mouth disease (HFMD) has caused public health concerns worldwide. We aimed to investigate the effect of meteorological factors on the HFMD epidemic in Qingdao, a port city in China. A total of 78641 cases were reported in Qingdao between January 2007 and December 2014. Of those, 71084 (90·39%) occurred in children aged 0–5 years, with an incidence of 1691·2/100000. The incidence increased from early spring, peaked between spring and summer, and decreased in late summer. Aetiological agents in all severe cases and selected mild cases were characterized by examining throat swabs. Except for enterovirus 71 (EV71) and coxsackievirus A16 (CA16), other EVs caused >50% of the HFMD cases between 2011 and 2014. EV71 was more frequent in the off-peak months than in the peak months and prone to causing more severe cases compared to CA16 (χ
2 = 46·3, P < 0·001). CA10 caused more severe HFMD than did CA6 (χ
2 = 20·49, P < 0·001) and all non-CA10 EVs (χ
2 = 41·01, P < 0·001). Community-derived HFMD cases accounted for 65·11%. Spearman rank correlation analysis showed that HFMD incidence in children aged 0–5 years was positively correlated with atmospheric temperature (r
= 0·77, P < 0·001), relative humidity (r
= 0·507, P < 0·001), and precipitation (r
= 0·328, P < 0·001). Climate changes and CA10 surveillance in communities should be integrated into the current prophylactic programme.