Cardiovascular diseases (CVDs) have continued to be a leading cause of death among adults. Civil servants constitute vital workforce, and high CVD burden in this group has implications for national productivity. Unfortunately, guided cardiovascular health education interventions are uncommon. This study assessed the effect of an educational intervention on knowledge and practice of CVD prevention among Nigerian civil servants. Quasi-experimental study design was employed among subjects in distant communities in Cross River State. Multistage technique was used to recruit 172 subjects into one control group (Ogoja) and two intervention groups (Calabar and Ikom). The first intervention group received 4-h daily, 5-day cardiovascular health education, with emphasis on burden, risk factors, and preventive measures including nutrition, stress, alcohol, medicals, exercise, and smoking. The second intervention group received the same content of education, but with the use of Food, Rest for stress management, Alcohol, Medicals, Exercise, and Smoking (FRAMES) as guide for delivery. Questionnaires were used to assess knowledge and practice at baseline and post-intervention. Data were analyzed using SPSS version 20.0. Knowledge scores and practice of CVD prevention were compared between study groups using inferential statistics. Mean age was 46.3 ± 7.4 years, and no significant difference in sociodemographic characteristics was observed by comparing the study groups (p > 0.05). Baseline knowledge and practice of preventive measures were generally poor, and no significant difference was observed by comparing the groups (p > 0.05). At 12 weeks post-intervention, knowledge of CVD was higher in the intervention groups compared with the control group (p < 0.05). Unlike control group, both intervention groups had improvement in physical exercise, medical screening, and fruit consumption (p < 0.05). There was no significant difference in postintervention knowledge and practice of CVD prevention by comparing both intervention groups (p > 0.05). For effective delivery of cardiovascular health education, the use of “FRAMES” is as effective as its nonuse. Further studies in other settings are recommended.