Objective To investigate the association of daily meteorological factors with mortality of cardiovascular disease (CVD) in Guangzhou city in order to provide scientific evidence for official authorities in medical meteorological forecast and in planning prevention and intervention strategies. Methods According to the daily CVD mortality statistics and meteorological data obtained from January 1, 2012 to December 31, 2013 in Guangzhou city, we investigated the relationship between daily meteorological factors, including daily mean atmosphere pressure, temperature(mean, maximal and minimal), relative humidity, rainfall, mean wind velocity and sunshine time, and mortality of CVD by using a distributed lag nonlinear model(DLNM) on ruling out the confounding factors basis. Results The daily deaths from CVD in Guangzhou city tended to increase in the past years, and the death was associated with daily mean atmosphere pressure, temperature, wind velocity, humidity, rainfall and sunshine time(all P<0.05). Daily mean air pressure was positively correlated with wind velocity(r>0), yet the temperature (mean, maximal and minimal), relative humidity and rainfall were negatively related to sunshine(r<0). Maximum RR was 1.051(95%CI:1.026-1.076) at the mean pressure being 1019hPa and lagged days of 30, and maximum RR, 1.036 (95%CI:1.024-1.048) at mean temperature being 6℃and lagged day of 6 to 8. Conclusion Health education is recommended in the residents in Guangzhou city and preventive measures to challenge the climate changes are necessary, because meteorological factors may lead to lagged effects on the mortality of cardiovascular disease.