OBJECTIVES: The Heart Outcomes Prevention Evaluation (HOPE) study showed significant mortality and morbidity benefits associated with ramipril in high-risk patients. Cardiac mortality was significantly reduced from 8.1% in placebo to 6.1% in ramipril (RR, 0.74; p<0.001). The objective of this study is to contrast multiple cost-effectiveness (CE) scenarios of ramipril in preventing CV events in high-risk patients. METHODS: Applying retrospective decision analytic technique, CE analysis from a payer perspective was conducted using direct medical costs of clinical events from the literature and efficacy data from the HOPE study. Expected cost was estimated using probabilities associated with fatal and non-fatal myocardial infarction, stroke and other CV events. CE analysis was conducted under three alternate scenarios of within-trial analysis based on cost and outcome during the trial period of 4.5 years, persistent benefit analysis based on the assumption of therapy being discontinued beyond trial period and an extended benefit analysis assuming patients continued on therapy beyond trial period. Based on life expectancy for a similar cohort reported in the literature, persistent-benefit of therapy was assumed for a period of 11.6 years. Extended benefits were obtained by extrapolating within trial efficacy beyond the study duration. CE analysis was conducted to estimate the ratio of incremental expected cost of ramipril therapy to the incremental life year gained (LYG). All costs were discounted at 3% per year. RESULTS: Discounted cost for within-trial CE analysis was $2600 for ramipril compared to $1554 for placebo (incremental cost, $1046). With a 2% absolute risk reduction in within-trial cardiac mortality, the incremental cost/LYG was $11,622. Cost/LYG under the persistent benefit was $4509. For extended benefit of therapy, cost/LYG was $4014. Sensitivity analysis ranged from cost/LYG of $3143 to $12,689. CONCLUSIONS: Ramipril is CE in preventing CV events in high-risk patients across multiple therapy benefit scenarios.