BackgroundSedentary behavior (SB) and physical activity (PA) are modifiable risk factors for cardiovascular disease (CVD); however, previous research on the effects of PA and SB on CVD has been relatively homogeneous. Our study investigated the association between PA, SB, and CVD-related outcomes.MethodsA comprehensive search strategy was conducted in the MEDLINE, Embase, Cochrane Library, and Web of Science databases from their inception to September 2022. We identified eligible studies according to PICOS: the populations comprised healthy adults, the interventions or exposures were PA or SB, the outcomes were CVD-related outcomes, and the study designs were randomized controlled trials (RCTs) and longitudinal studies (LS). Outcomes were pooled using fixed or random effects models, and the quality of individual studies was assessed by the Cochrane Risk of Bias Instrument and the Newcastle Ottawa Scale.ResultsA total of 148 RCTs and 36 LS were included, comprising a total of 75,075 participants. The study quality was rated as low to moderate. We found an increased hazard ratio (HR) for CVD in the population with SB (HR = 1.34; 95% confidence interval [CI]: 1.26 to 1.43; I2 = 52.3%; Pheterogeneity < 0.001, random model) and a decreased HR for CVD in those who performed long-term PA (HR = 0.71; 95% CI: 0.66 to 0.77; I2 = 78.0%, Pheterogeneity < 0.001, random model). Long-term PA improved the lipid profiles in healthy adults; participants in this group exhibited increased high-density lipoprotein (weighted mean difference [WMD] = 2.38; 95% CI: 1.00 to 3.76; I2 = 84.7%; Pheterogeneity < 0.001, random model), decreased triglycerides (WMD = −7.27; 95% CI: −9.68 to −4.87; I2 = 0%, Pheterogeneity = 0.670, fixed model), and lower total-cholesterol (WMD = −6.84; 95% CI: −9.15 to −4.52; I2 = 38.4%, Pheterogeneity < 0.001, random model).ConclusionsLong-term SB increases the risk of CVD in healthy adults, whereas PA reduces the risk of CVD and improves indicators associated with CVD. However, the ability of PA to improve blood lipids appeared to be limited. The detailed association of SB and PA on CVD needs to be further investigated in the future.