Hourly peak concentration may capture health effects of ambient fine particulate matter pollution (PM2.5) better than daily averages. We examined the associations of hourly peak concentration of PM2.5 with cardiovascular mortality in Guangzhou, China. We obtained daily data on cardiovascular mortality and hourly PM2.5 concentrations in Guangzhou from 19 January 2013 through 30 June 2015. Generalized additive models were applied to evaluate the associations with adjustment for potential confounding factors. Significant associations were found between hourly peak concentrations of PM2.5 and cardiovascular mortality, particularly from ischemic heart diseases (IHD) and cerebrovascular diseases (CBD). Every 10 μg/m3 increment of hourly peak PM2.5 at lag 03 day was associated with a 1.15% (95% CI: 0.67%, 1.63%); 1.02% (95% CI: 0.30%, 1.74%) and 1.09% (95% CI: 0.27%, 1.91%) increase in mortalities from total cardiovascular diseases, IHD and CBD, respectively. The effects remained after adjustment for daily mean PM2.5 and gaseous air pollutants, though there was a high correlation between PM2.5 peak and PM2.5 mean (correlation coefficient = 0.95). No significant association was observed for acute myocardial infarction (AMI). In addition to daily mean concentration of PM2.5, hourly peak concentration of PM2.5 might be one important risk factor of cardiovascular mortality and should be considered as an important air pollution indicator when assessing the possible cardiovascular effects of PM2.5.