Background Data regarding the volume of exercise and presence of subclinical atherosclerosis are conflicting. We performed a systematic review and meta-analysis to assess the effect of volume of exercise on all-cause mortality and coronary artery calcification (CAC). Methods We systematically searched MEDLINE, EMBASE and CINAHL (inception to May 2019) with relevant keywords and MeSH headings for exercise and subclinical atherosclerosis. Two reviewers independently extracted data and assessed risk of bias. Data were pooled using fixed or random effect models as appropriate. We evaluated the overall quality of evidence using GRADE. Results From 5424 citations screened, 5 met inclusion criteria, comprising 36,646 patients. There were no randomized controlled trials (RCTs). The mean age was 50.6 (±11) and 68% were male. The authors’ categorization of exercise intensity and interpretation of self-reported data varied considerably. High-volume exercise was associated with significantly lower all-cause mortality as compared to low volume (odds ratio 0.64, 95% confidence interval CI 0.51–0.82, I2=0%). There was no difference in the presence of CAC<100 Agatston Units (AU) (OR 1.57, 95%CI 0.85–2.89, I2=95%) nor in CAC>100 AU (OR 1.25, 95%CI 0.8–1.94, I2=85%). The overall quality of the evidence was low. Conclusion Observational studies suggest that high volume exercise is associated with significant reductions in all-cause mortality. RCTs are required to confirm these findings. [Figure presented]