Researchers have reported statistically significant associations between air pollutants and cardiovascular disease (CVD). However, few studies have investigated the acute cardiovascular effects of joint exposure to Ozone (O3) and fine particulate matter (PM2.5) in a location so distinctive like Harris County. The objective of this study was to investigate the association between the joint exposure to O3 and PM2.5, and emergency room diagnosis of CVD, in Harris County, Texas. Data used include all emergency room (ER) visits, and O3 and PM2.5 levels in the same years. Logistic regression modeled the effect of temperature, relative humidity, wind speed, wind, ozone, and fine particulate matter, averaged by day. Three models were estimated for all visits, visits during the months of April and September of 2005 and 2009, and for visits for patients from zip codes that are close to monitoring stations. A 1 μg/m3 increase in PM2.5 was associated with a 0.4% increase in the odds of cardiovascular disease emergency room diagnoses on the same day (p-value < 0.001), and a 0.2% increase in the odds of cardiovascular disease emergency room diagnoses on the following day (p-value < 0.001). This study demonstrated that there are statistically significant associations between ER visits for CVD diagnosis in Harris County, with joint exposure to O3 and PM2.5 of the same day and previous day. The increase of CVD cases as well as association between humidity and the numbers of CVD cases, males and blacks has higher odds.