Background Acute infections are known cardiovascular disease ( CVD ) triggers, but little is known regarding how CVD risk varies following inpatient versus outpatient infections. We hypothesized that in‐ and outpatient infections are associated with CVD risk and that the association is stronger for inpatient infections. Methods and Results Coronary heart disease (CHD) and ischemic stroke cases were identified and adjudicated in the ARIC (Atherosclerosis Risk in Communities Study). Hospital discharge diagnosis codes and Medicare claims data were used to identify infections diagnosed in in‐ and outpatient settings. A case‐crossover design and conditional logistic regression were used to compare in‐ and outpatient infections among CHD and ischemic stroke cases (14, 30, 42, and 90 days before the event) with corresponding control periods 1 and 2 years previously. A total of 1312 incident CHD cases and 727 incident stroke cases were analyzed. Inpatient infections (14‐day odds ratio [ OR ]=12.83 [5.74, 28.68], 30‐day OR =8.39 [4.92, 14.31], 42‐day OR =6.24 [4.02, 9.67], and 90‐day OR =4.48 [3.18, 6.33]) and outpatient infections (14‐day OR =3.29 [2.50, 4.32], 30‐day OR =2.69 [2.14, 3.37], 42‐day OR =2.45 [1.97, 3.05], and 90‐day OR =1.99 [1.64, 2.42]) were more common in all CHD case periods compared with control periods and inpatient infection was a stronger CHD trigger for all time periods ( P <0.05). Inpatient infection was also a stronger stroke trigger with the difference borderline statistically significant ( P <0.10) for the 42‐ and 90‐day time periods. Conclusions In‐ and outpatient infections are associated with CVD risk. Patients with an inpatient infection may be at particularly elevated CVD risk and should be considered potential candidates for CVD prophylaxis.