With the rapid and widespread adoption of mobile devices, mobile phones offer an opportunity to deliver cardiovascular disease (CVD) interventions. This study evaluated the efficacy of a mobile phone-based lifestyle intervention aimed at reducing the overall CVD risk at a health management center in Guangzhou, China. We recruited 589 workers from eight work units. Based on a group-randomized design, work units were randomly assigned either to receive the mobile phone-based lifestyle interventions or usual care. The reduction in 10-year CVD risk at 1-year follow-up for the intervention group was not statistically significant (-1.05%, p = 0.096). However, the mean risk increased significantly by 1.77% (p = 0.047) for the control group. The difference of the changes between treatment arms in CVD risk was -2.83% (p = 0.001). In addition, there were statistically significant changes for the intervention group relative to the controls, from baseline to year 1, in systolic blood pressure (-5.55 vs. 6.89 mmHg; p < 0.001), diastolic blood pressure (-6.61 vs. 5.62 mmHg; p < 0.001), total cholesterol (-0.36 vs. -0.10 mmol/L; p = 0.005), fasting plasma glucose (-0.31 vs. 0.02 mmol/L; p < 0.001), BMI (-0.57 vs. 0.29 kg/m(2); p < 0.001), and waist hip ratio (-0.02 vs. 0.01; p < 0.001). Mobile phone-based intervention may therefore be a potential solution for reducing CVD risk in China.