Practice-level evidence is needed to clarify the value of population-based clinical decision support (CDS) tools in reducing racial and sex disparities in cardiovascular care. To evaluate the association between CDS tools and racial and sex disparities in the aspirin use, blood pressure control, cholesterol management, and smoking cessation (ABCS) care quality metrics among smaller primary care practices. This cross-sectional study used practice-level data from the Agency for Healthcare Research and Quality-funded EvidenceNOW initiative. The national initiative from May 1, 2015, to April 30, 2021, spanned 12 US states and focused on improving cardiovascular preventive care by providing quality improvement support to smaller primary care practices. A total of 576 primary care practices in EvidenceNOW submitted both survey data and electronic health record (EHR)-derived ABCS data stratified by race and sex. Practice-level estimates of disparities between Black and White patients and between male and female patients were calculated as the difference in proportions of eligible patients within each practice meeting ABCS care quality metrics. The association between CDS tools (EHR prompts, standing orders, and clinical registries) and disparities was evaluated by multiply imputed multivariable models for each CDS tool, adjusted for practice rurality, ownership, and size. Across the 576 practices included in the analysis, 219 (38.0%) had patient panels that were more than half White and 327 (56.8%) had panels that were more than half women. The proportion of White compared with Black patients meeting metrics for blood pressure (difference, 5.16% [95% CI, 4.29%-6.02%]; P < .001) and cholesterol management (difference, 1.49% [95% CI, 0.04%-2.93%] P = .04) was higher; the proportion of men meeting metrics for aspirin use (difference, 4.36% [95% CI, 3.34%-5.38%]; P < .001) and cholesterol management (difference, 3.88% [95% CI, 3.14%-4.63%]; P < .001) was higher compared with women. Conversely, the proportion of women meeting practice blood pressure control (difference, -1.80% [95% CI, -2.32% to -1.28%]; P < .001) and smoking cessation counseling (difference, -1.67% [95% CI, -2.38% to -0.95%]; P < .001) metrics was higher compared with men. Use of CDS tools was not associated with differences in race or sex disparities except for the smoking metric. Practices using CDS tools showed a higher proportion of men meeting the smoking counseling metric than women (coefficient, 3.82 [95% CI, 0.95-6.68]; P = .009). The findings of this cross-sectional study suggest that practices using CDS tools had small disparities that were not statistically significant, but CDS tools were not associated with reductions in disparities. More research is needed on effective practice-level interventions to mitigate disparities.