IMPORTANCE: Management of cardiovascular disease (CVD) risk in socioeconomically vulnerable patients is suboptimal; better risk factor control could improve CVD outcomes. OBJECTIVE: To evaluate the impact of a clinical decision support system (CDSS) targeting CVD risk in community health centers (CHCs). DESIGN, SETTING, AND PARTICIPANTS: This cluster randomized clinical trial included 70 CHC clinics randomized to an intervention group (42 clinics; 8 organizations) or a control group that received no intervention (28 clinics; 7 organizations) from September 20, 2018, to March 15, 2020. Randomization was by CHC organization accounting for organization size. Patients aged 40 to 75 years with (1) diabetes or atherosclerotic CVD and at least 1 uncontrolled major risk factor for CVD or (2) total reversible CVD risk of at least 10% were the population targeted by the CDSS intervention. INTERVENTIONS: A point-of-care CDSS displaying real-time CVD risk factor control data and personalized, prioritized evidence-based care recommendations. MAIN OUTCOMES AND MEASURES: One-year change in total CVD risk and reversible CVD risk (ie, the reduction in 10-year CVD risk that was considered achievable if 6 key risk factors reached evidence-based levels of control). RESULTS: Among the 18 578 eligible patients (9490 [51.1%] women; mean [SD] age, 58.7 [8.8] years), patients seen in control clinics (n = 7419) had higher mean (SD) baseline CVD risk (16.6% [12.8%]) than patients seen in intervention clinics (n = 11 159) (15.6% [12.3%]; P < .001); baseline reversible CVD risk was similarly higher among patients seen in control clinics. The CDSS was used at 19.8% of 91 988 eligible intervention clinic encounters. No population-level reduction in CVD risk was seen in patients in control or intervention clinics; mean reversible risk improved significantly more among patients in control (-0.1% [95% CI, -0.3% to -0.02%]) than intervention clinics (0.4% [95% CI, 0.3% to 0.5%]; P < .001). However, when the CDSS was used, both risk measures decreased more among patients with high baseline risk in intervention than control clinics; notably, mean reversible risk decreased by an absolute 4.4% (95% CI, -5.2% to -3.7%) among patients in intervention clinics compared with 2.7% (95% CI, -3.4% to -1.9%) among patients in control clinics (P = .001). CONCLUSIONS AND RELEVANCE: The CDSS had low use rates and failed to improve CVD risk in the overall population but appeared to have a benefit on CVD risk when it was consistently used for patients with high baseline risk treated in CHCs. Despite some limitations, these results provide preliminary evidence that this technology has the potential to improve clinical care in socioeconomically vulnerable patients with high CVD risk. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03001713.