Determining the pretest probability of angiographically significant (≥50% stenosis) coronary artery disease (CAD) in symptomatic patients relies on the Diamond and Forrester (DF) classification, which was derived from a cohort referred for invasive coronary angiography. The accuracy of this approach in patients referred for noninvasive coronary angiography is not fully known. Consecutive patients without known CAD referred for coronary computed tomographic angiography (CCTA) were evaluated. Chest pain was prospectively categorized as nonanginal, atypical angina, typical angina, or asymptomatic. The pretest likelihood of angiographically significant CAD was estimated using DF classification and compared with observed rates of angiographically significant CAD on CCTA. Among 1,027 patients (41% women; mean age 50 ± 12 years), 38 (4%) had nonanginal symptoms, 643 (63%) had atypical angina, 72 (7%) had typical angina, and 274 (26%) were asymptomatic. The prevalence of angiographically significant CAD in patients with nonanginal chest pain, atypical angina, typical angina, and no symptoms was 1 (3%), 55 (9%), 14 (19%), and 25 (9%), respectively (p <0.001). DF classification significantly overestimated angiographically significant CAD prevalence across all symptom classifications, genders, and ages despite adjustment for risk factors (p <0.001 for all comparisons). DF classification had an area under the receiver-operating characteristic curve of 0.72 (95% confidence interval 0.66 to 0.78), which was not significantly different from age alone (0.69) or age, symptoms, and risk factors (0.68). In conclusion, in a low- to intermediate-risk cohort referred for CCTA, DF classification significantly overestimated angiographically significant CAD prevalence across all age, gender, and symptom strata. The DF classification may overestimate the pretest probability of angiographically significant CAD in contemporary patients referred for CCTA.