Background: The prevalence of cardiovascular diseases (CVD) is continuously increasing. A nurse-led workplace health promotion program (NWHPP) has demonstrated potential in reducing cardiovascular risks among employees. This study aimed to evaluate the effectiveness of the NWHPP in reducing CVD risks among at-risk workers. Methods: Sixty workers from 2 factories in Thailand, each with an estimated 10-year cardiovascular risk of 5% or higher (determined by the WHO/ISH cardiovascular risk prediction chart), were enrolled. Participants were randomly assigned to either the intervention or control group based on their factory. The intervention group received an 8-week program comprising 3 core components: redesigning healthcare services, strengthening self-management, and obtaining organizational support. Evaluations of the estimated 10-year CVD risk, systolic blood pressure (SBP), smoking status, and body mass index (BMI) were conducted at baseline and at 1- and 3-month follow-ups. Results: The intervention group showed significant improvements compared to the control group in CVD risk score ( F = 4.827, P = .017) and SBP ( F = 12.136, P < .001). Moreover, non-smokers were significantly higher in the intervention group (75.0%) compared with the control group (46.2%) after the 3-month follow-up (OR = 3.50; 95%CI 1.11-11.07; P = .030). However, BMI differences between the groups were not statistically significant. Conclusion: The nurse-led workplace health promotion program effectively improved cardiovascular risk scores among at-risk workers. Developing workplace policies and environments that promote healthy behaviors is essential for reducing CVD risks among at-risk workers.