Background Vascular alterations induced by antineoplastic treatment might be considered as a possible underlying mechanism of increased cardiovascular (CV) sequelae in childhood cancer survivors (CCS). Therefore, we thought to evaluate the changes in arterial stiffness (AS) among long-term CCS compared to the general population. Methods AS was assessed by digital photoplethysmography (Stiffness Index (SI); m/s) among 1,002 participant of “Cardiac and Vascular late Sequelae in long-term Survivors of childhood cancer” study, diagnosed with neoplasia prior to an age of 15 years (1980–1990). A population-based subsample from the Gutenberg Health Study (GHS) (n = 5,252) was used for comparison. All subjects underwent a comprehensive, standardized clinical examination in the same study center. Results Compared to the population subsample with similar age range, CCS had higher SI in multivariable linear regression analysis with adjustment for cardiovascular risk factor and comorbidities (β = 0.660.51/0.80; p < 0.0001). Moreover, SI was varying according to tumor entity with highest values in bone tumors. Interestingly, CCS demonstrated stiffer vessels than individuals from the population even in absence of a history of chemo- or radiotherapy (β = 0.560.16/0.96; p = 0.0066) or prevalent hypertension (β = 0.660.50/0.81; p < 0.0001) in fully-adjusted models. Finally, a 5.2-fold 3.9; 7.0 higher prevalence of SI values exceeding age-specific, population-based reference limits was observed among CCS compared to individuals from the population. Conclusions This is the first study demonstrating increased AS among long-term CCS. The data suggest that AS promotion might differ in individuals with childhood cancer: Cancer development and antineoplastic treatment might be relevant determinants.