OBJECTIVES: We attempted to determine the prognostic value of coronary computed tomographic angiography (CTA) in patients with inconclusive functional stress tests. BACKGROUND: Patients with suspected coronary artery disease (CAD) and inconclusive noninvasive cardiac stress tests represent a frequent management challenge. METHODS: We examined 529 consecutive patients with suspected CAD and prior inconclusive functional stress tests. All patients underwent a coronary CTA scan using a 64-slice multidetector row scanner. CAD severity by coronary CTA was categorized as: 1) no evidence of CAD; 2) nonobstructive coronary plaques (< 30%); 3) mild stenosis (30% to 49%); 4) moderate stenosis (50% to 69%); and 5) severe stenosis (≥ 70%). Patients were also categorized according to a modified Duke prognostic CAD index. Survival analyses were performed using Cox proportional hazards models adjusted for baseline risk factors and coronary artery calcium score. The primary outcome of the study was the combined endpoint of all-cause mortality and nonfatal myocardial infarction. RESULTS: Among patients with inconclusive stress tests, the large majority (69%) did not demonstrate significant CAD by coronary CTA. During a mean follow-up of 30.1 ± 11.1 months, there were 20 (3.8%) deaths and 17 (3.2%) nonfatal myocardial infarctions. Multivariable Cox regression analysis revealed that the presence of increasing degrees of obstructive CAD by CTA was an independent predictor of adverse events (hazard ratio [HR]: 1.66 [95% confidence interval (CI): 1.23 to 2.23], p = 0.001). Indeed, the presence of ≥ 50% coronary stenosis was associated with an increased risk of events (HR: 3.15 [95% CI: 1.26 to 7.89], p = 0.01). Likewise, the Duke prognostic CAD index was also found to be an independent predictor of events (HR: 1.54 [95% CI: 1.20 to 1.97], p = 0.001). CONCLUSIONS: Among patients with inconclusive functional stress tests, the noninvasive assessment of CAD severity by coronary CTA has been shown to provide incremental prognostic information beyond the evaluation of traditional risk factors and coronary artery calcium score.