OBJECTIVES: To compare the cost-effectiveness of the vasodilator stress agents, adenosine and dipyridamole, in subjects with known or suspected coronary artery disease (CAD) undergoing technetium-99m sestamibi single photon computed tomography (SPECT) imaging in a prospective, randomized trial from a hospital perspective. METHODS: Direct medical costs (standardized to 2001 US dollars) of the vasodilator stress agents, adverse effects and monitoring were included. To determine the effectiveness of adenosine and dipyridamole, the overall accuracy of each agent was calculated as follows: (number of true-positive results+number of true-negative results)/(total number of tests), using cardiac catheterization as the gold standard for comparison. The incremental cost-effectiveness ratio (ICER) was calculated as follows: (total cost of adenosine-total cost of dipyridamole)/(overall accuracy of adenosine-overall accuracy of dipyridamole). One-way sensitivity analysis was conducted, varying the costs of adenosine, dipyridamole, adverse effects and monitoring. RESULTS: Baseline demographics, including gender, age, co-morbidities and number of diseased vessels were similar between the groups (p>0.05 for all comparisons). With adenosine (n=49) sensitivity, specificity and overall accuracy was 82% (32/39), 60% (6/10) and 78% (38/49), respectively. The sensitivity, specificity and overall accuracy for dipyridamole was 68% (34/50), 67% (6/9) and 68% (40/59), respectively (p>0.05 for all comparisons with adenosine). The incidence of adverse events was 43% with adenosine and 12% with dipyridamole (p<0.001). The mean cost of the vasodilator stress agent was $154+/127 with adenosine and $10+/-2 with dipyridamole (p<0.001). When the cost of adverse effects and monitoring was included, the total cost rose to $160+/-27 and $19+/-3 with adenosine and dipyridamole, respectively (p<0.001). The ICER was $1,410 (sensitivity analysis: $1,390-$1,676) for each additional correctly identified case with adenosine. CONCLUSIONS: In a randomized trial of patients referred for vasodilator stress using technetium-99m sestamibi SPECT imaging, data indicate that adenosine is more expensive but more effective than dipyridamole in CAD detection.