Coronary artery calcium scoring (CAC) has garnered attention in the diagnostic approach to chest pain patients. However, little is known about the interplay between zero CAC, sex, race, ethnicity, and quantitative coronary plaque analysis. We conducted a retrospective analysis from our computed tomography registry of patients with stable angina without prior myocardial infarction or revascularization undergoing coronary computed tomography angiography at Montefiore Healthcare System. Follow-up end points collected included invasive angiography, type-1 myocardial infarction, coronary revascularization, cardiovascular and all-cause death. A total of 2249 patients were included (66% female). The median follow-up was 5.5 years. The median age of those without CAC was 52 years (interquartile range, 44-59) and 60 years (interquartile range, 53-68) in those with CAC. Most patients were Hispanic (58%), and the rest were non-Hispanic Black (28%), non-Hispanic White (10%), and non-Hispanic Asian (5%). The majority had CAC=0 (55%). The negative predictive value of CAC=0 was 92.8%, 99.9%, and 99.9% for any plaque, obstructive coronary artery stenosis, and the composite outcome of all-cause death, myocardial infarction, or coronary revascularization, respectively. Among patients without CAC (n=1237), 89 patients (7%) had evidence of plaque on their coronary computed tomography angiography with a median low-attenuation noncalcified plaque burden of 4% (2-7). There were no significant differences in the negative predictive value for CAC=0 by sex, race, or ethnicity. Patients with ≥2 risk factors had higher odds of having plaque with zero CAC. In summary, no sex, race, or ethnicity differences were demonstrated in the negative predictive value of a zero CAC; however, patients with ≥2 risk factors had a higher prevalence of plaque. A small percentage (7%) of symptomatic patients undergoing coronary computed tomography angiography with zero CAC had noncalcified coronary plaque, with the implication that caution is needed for downscaling of preventive treatment in patients with zero CAC, chest pain, and multiple risk factors.