Previous studies have demonstrated that acute systemic inflammation after surgery or infection is associated with a transient increase in the risk of vascular events. This suggests that vascular risk is not stable but fluctuates within short periods in response to inflammatory stimuli. While an association between respiratory tract infection and vascular events is well-documented, the effects of other acute infections and inflammatory stimuli are less certain. The principal aim of this project was to investigate further the role of acute inflammation and infection in vascular disease, employing the unique opportunities offered by electronic health record databases. Two large observational studies were undertaken. First, the self-controlled case series method and Medicaid claims data from the United States were used to examine the short-term effects of invasive dental treatment, a novel acute inflammatory model, on the risk of vascular events. Second, a matched case-control study using primary care data from the United Kingdom General Practice Research Database investigated the role of acute maternal infection in the development of pre-eclampsia – a vascular disorder of pregnancy. The case series analysis of 1152 adults with a vascular event demonstrated a transiently increased vascular event rate in the four weeks after invasive dental treatment relative to unexposed time periods. The analysis of 1533 pre-eclampsia cases and 14236 controls who had completed a pregnancy without pre-eclampsia revealed an increased risk of pre-eclampsia associated with antibiotic prescriptions and urinary infection, but not respiratory infection, during pregnancy. The findings suggest that exposures sufficient to produce an acute inflammatory response may play an important role in the occurrence of vascular outcomes. Future research on the effects of other acute inflammatory triggers and the mediating mechanisms involved should help establish a clearer role for acute inflammation and infection in vascular disease and inform preventative strategies during periods of increased vascular risk.