Abstract Background Cardiorespiratory fitness (CRF) and coronary plaque burden are both important predictors of mortality. Although mortality of coronary heart disease (CHD) is reduced, prevalence remains high and there is a need to improve early detection and preventive measures. How CRF relates to coronary plaque burden and composition in the general population is largely unknown. Purpose The aim was to study the relationship between CRF and the total coronary plaque burden, including subgroups of coronary plaques, in subjects without known CHD. Methods A random sample of participants from a large population-based echocardiographic reference range study aged 55-70 at baseline was included. Coronary plaque burden was assessed, on average, 4.0 years after the baseline evaluation using coronary computed tomography angiography (CCTA). The burden and characteristics of the coronary plaques were evaluated using a validated, commercially available, semi-automatic software that assessed all coronary territories including the left main, left anterior descending, circumflex, and right arteries. Coronary plaques were classified as dense calcified plaques, plaques with necrotic core, fibrous, and fibrous-fatty plaques. Baseline measures included cardiovascular risk factor assessment and measurement of peak oxygen consumption (VO2peak) assessed by treadmill cardiopulmonary exercise testing. Linear regression models were used to assess the impact of VO2peak on coronary plaque burden. In Model 1, we adjusted for sex and age, while Model 2 also included adjustments for non-HDL cholesterol, HbA1c, systolic blood pressure, smoking status, and body mass index. Results Of 845 invited to undergo CCTA, 707 (51% females) underwent CT scanning. Of these, 699 scans had acceptable quality for further analyses. Table 1 shows baseline characteristics and Table 2 shows the associations of VO2peak with coronary plaque burden. In the fully adjusted Model 2, there was a significant negative association of VO2peak with total plaque burden (β -0.18, R2 15%, p<0.001), while the association was not significant in Model 1 (p=0.54). Similarly, higher VO2peak significantly predicted a lower burden of dense calcified plaques, plaques with necrotic core, and fibrofatty plaques in both models (R2 3-17%, p≤0.01). The results were consistent whether the coronary plaques were evaluated across the entire coronary arteries (down to a diameter of 1.5 mm) or solely in the proximal segments. However, the predictive power of the models was relatively low with R2 of maximum 17%. Conclusion In a population without known CHD, CRF explained a modest part of the variation in coronary plaque burden. Considering CRF in risk prediction may enhance coronary artery disease prevention beyond traditional risk factors.