<p><i>Purpose</i> To systemically evaluate current evidence on the association between non-invasively monitored atherosclerosis progression and adverse cardiovascular outcomes, assessing its potential as a surrogate endpoint for clinical trials. <i>Methods</i> PubMed, Embase, and Cochrane Library were searched from 1988 to 2024 to locate studies. Bias was assessed using the Newcastle-Ottawa Scale. Multivariable-adjusted hazard ratios (aHR) were included in a random-effects meta-analysis with modality-specific estimates. Between-study heterogeneity was quantified using I². <i>Results</i> Thirty-four observational studies were included with an aggregate sample size of 56,189 participants (mean age: 60 ± 10 years; females: 44%). Carotid ultrasound plaque progression (n = 4,727) showed a consistent association with outcome (aHR: 1.38 (95% CI: 1.08–1.77), P = 0.009); however, heterogeneity was high (I² = 95.7%). Conversely, conflicting results were found between carotid intima-media thickness progression and outcome. Non-contrast computed tomography of coronary calcification progression (n = 27,067; aHR: 1.61 (95% CI: 1.30–1.99), P &lt; 0.001; I² = 83.9%) and aortic calcification progression (n = 10,916; aHR: 1.50 (95% CI: 1.02–2.23), P = 0.042; I² = 66.1%) were independently associated with outcome, despite high heterogeneity. Evidence on coronary plaque progression on computed tomography angiography was inconclusive due to low-quality studies. <i>Conclusion</i> Atherosclerosis progression, assessed by ultrasound or computed tomography, in the carotids, coronaries, and aorta was independently associated with cardiovascular outcomes, despite substantial between-study heterogeneity. Highest-quality evidence was found for carotid ultrasound plaque progression and coronary and aortic calcification progression on non-contrast computed tomography. Still, large-scale studies are warranted to identify the optimal surrogate for clinical trials.</p> Graphical Abstract <p></p>