Studies have shown the health benefits of cigarette smoking cessation. However, the literature remains unclear about the relationship between smoking reduction and health risks. This comprehensive review and meta-analysis updates previous reviews with the newest estimates. We conducted a systematic review and meta-analysis evaluating the association between smoking reduction and some health risks in observational studies. We defined the following smoking categories: heavy smokers smoked ≥15-20 cigarettes per day (CPD), moderate smokers smoked 10-19 CPD, and light smokers smoked <10 CPD. The relative risks (RRs) and 95% confidence intervals (CIs) were estimated using random-effect models. We identified 19 studies including four case-control and 15 cohort studies. Compared with continuing heavy smokers, we found decreased lung cancer risk for those who reduced CPD by more than 50% (RR = 0.72, 95% CI: 0.52, 0.91), from heavy to moderate (RR = 0.66, 95% CI: 0.46, 0.85), and from heavy to light (RR = 0.60, 95% CI: 0.49, 0.72). We also found lower risk of cardiovascular disease (CVD) for those who reduced from heavy to light smoking (RR = 0.78, 95% CI: 0.67, 0.89) but not those who reduced by more than 50% and reduced smoking from heavy to moderate. We did not find any significant difference in all-cause mortality, all-cancer risks, and smoking-/tobacco-related cancer risk among those who reduced. Substantial smoking reduction may decrease lung cancer risk but results on CVD (coronary heart disease and stroke combined) risk were mixed. The relationships between smoking reduction and other endpoints examined were not significant. This meta-analysis helps clarify our understanding of various smoking reduction levels on some health risks. While smoking reduction may decrease risks of lung cancer, the relationships between smoking reduction and other endpoints, including all-cause mortality and cardiovascular disease, remain unclear. Although smoking reduction may decrease lung cancer risks, the magnitude of lung cancer risk remain high. Among smokers, complete cessation remains the most effective approach for cancer and CVD prevention.