Background: Wald and law in their landmark paper published in BMJ in 2003 hypothesized that the use of fixed dose combination of statins, beta blockers, angiotensin-converting-enzyme inhibitor (ACE) inhibitor, and aspirin (Pollypill) may decrease cardiovascular disease by >80% if Pollypills are used as primary prevention. Many clinical trials were started to test this hypothesis. The present systematic review and meta-analysis aims to assess the available clinical trials to see the effect of Pollypill on cardiovascular mortality and on other risk factors that linked with increase in cardiovascular events. Materials and methods: Available databases were searched with different specific terms and combination of key words. All randomized clinical trials exploring the effect of Pollypill on various cardiovascular parameters were included in the analysis. Primary endpoints as decided were cardiovascular mortality, systolic blood pressure, diastolic blood pressure, and low-density lipoprotein (LDL) cholesterol. Effect of Pollypill on high-density lipoprotein (HDL) cholesterol, total cholesterol, triglycerides, the number of participants who discontinued treatment, and the number of participants who experienced side effects were measured and analyzed as secondary outcomes. Both fixed and random models were used for analysis. Analysis was performed by comprehensive meta-analysis software. Results: Six trials were included in systematic review. It was observed that Pollypill decreases systolic and diastolic blood pressure (P ¼ 0.000). Pollypill was also found to decrease LDL cholesterol, total cholesterol, and triglyceride as compared to the control (all P ¼ 0.000); however, there was no significant improvement in HDL (P ¼ 0.39). The number of participants in whom side effects were observed were found to be more in the Pollypill group (odds ratio ¼ 1.73, P ¼ 0.000). It was also observed that dropouts were more in the Pollypill group than in the control group (odds ratio ¼ 1.48, P ¼ 0.02). Due to the lack of sufficient data effect of Pollypill, cardiovascular mortality could not be assessed. Conclusion: Pollypill decreases various surrogate endpoints related to cardiovascular outcome, but with the increased chance of side effects as compared to control.