Background <p>Today, nurses play a major role in cardiac rehabilitation programs. In this analysis, we aimed to systematically show the impact of nurse-led intervention on the cardiovascular risk factors in patients with coronary artery disease (CAD) using data from both randomized trials and observational studies.</p> Methods <p>Studies comparing a nurse-led interventional program versus a control group (no follow-up by nurses) based on the cardiovascular risk factors in patients with CAD were searched through online databases. Statistical analysis was carried out by the Revman software. Risk ratio (RR) with 95% confidence intervals (CI) and Weight mean difference (WMD) with 95% CI were used during data analysis.</p> Results <p>This study consisted of a total number of 2634 participants. In the nurse led interventional group, patients were regularly checked, counseled about proper diet and regular timely medications intake, lifestyle modifications and integration of regular exercise were also encouraged. In addition, regular blood tests were carried out to verify the efficacy of treatment and advice were given appropriately. Such an intervention was absent in the usual care group. Our results showed that in the nurse-led intervention group, when the parameters were compared at baseline versus during the follow-up period, total cholesterol {TC} (WMD: -0.63, 95% CI: - [0.97 – 0.30]; <i>P</i> = 0.0002), low density lipoprotein {LDL} (WMD: -0.61, 95% CI: - [0.92 – 0.30]; <i>P</i> = 0.0001) and systolic blood pressure {SBP} (WMD: - 7.04, 95% CI: - [13.4 – 0.68]; P = 0.03) were significantly decreased at follow-up favoring the nurse-led intervention. High density lipoprotein {HDL} levels (WMD: 0.06, 95% CI: 0.03 – 0.09; <i>P</i> = 0.0005) were also significantly increased at follow-up still in favor of this nurse-led intervention. However, there was no change in triglyceride (TG) level, diastolic blood pressure (DBP), body mass index (BMI) and waist circumference. In addition, our current results showed that exercise adherence (RR: 0.64, 95% CI: 0.06 – 1.34; <i>P</i> = 0.0005) was significantly more apparent in the nurse-led intervention group compared to the usual care group. Moreover, smoking cessation (RR: 0.79, 95% CI: 0.62 – 1.00; <i>P</i> = 0.05) was significantly observed in the nurse-led interventional group compared to the usual care group.</p> Conclusions <p>The nurse-led intervention had a positive impact on the cardiovascular risk factors in patients with CAD. Significantly improved lipid levels and SBP were observed as well as more adherence to regular physical activities and smoking cessation were observed in the nurse-led interventional group. Therefore, a nurse-led intervention might be more beneficial compared to the usual care to improve cardiovascular risk factors and thus preventing cardiovascular complications in patients with CAD. However, due to the several limitations of this analysis, further larger studies are required to confirm this hypothesis.</p>