Background <p>The coronary artery calcium (CAC) score is a validated imaging biomarker enhancing cardiovascular risk stratification in patients with type 2 diabetes mellitus (T2DM). However, residual risk persists, particularly among patients with moderate CAC scores. Diabetic retinopathy (DR), a microvascular complication of diabetes, may reflect systemic vascular vulnerability and provide additional prognostic information.</p> Methods <p>This observational cohort study was conducted as part of the primary prevention ACCoDiab study. 424 patients with T2DM (175 females and 249 males, with a mean age of 61 years) and no history of cardiovascular events underwent CAC scoring and clinical assessments, including DR screening. Patients were monitored for seven years or until the first cardiovascular events, including nonfatal myocardial infarction, ischemic stroke, hospitalization for heart failure, peripheral artery disease revascularization, and cardiovascular death. Cox regression, Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curves, and net reclassification improvement (NRI) were used to evaluate the added prognostic value of DR to CAC scoring and to develop a simple integrated cardiovascular risk score.</p> Results <p>Fifty patients (11.8%) had incident cardiovascular events. DR was significantly more prevalent among those who experienced events (58% vs. 25%, <i>p</i> &lt; 0.001). Both CAC score and DR were independently associated with cardiovascular events. When incorporating DR into the CAC-based risk model, the predictive power was significantly enhanced AUC 75 [0.69–0.82] vs. 68 [0.61–0.75], <i>p</i> = 0.01). Further improvement was observed after adjusting for traditional risk factors (AUC 79 [0.73–0.86] vs. 73 [0.66–0.81], <i>p</i> = 0.04). The presence of DR reclassified a significant proportion of patients into higher-risk categories, particularly those with low and moderate CAC scores. Additionally, the severity of DR was also found to provide incremental prognostic information but did not provide significant additional stratification beyond the binary presence of DR.</p> Conclusion <p>The combination of diabetic retinopathy and CAC score significantly enhances cardiovascular risk stratification in T2DM patients, beyond traditional risk factors, highlighting that both microvascular and macrovascular factors should be considered in comprehensive cardiovascular risk assessment. This approach, integrated to clinical routine, may help identify patients for earlier intervention and more personalized treatment strategies.</p> <p><i>Trial registration</i> NCT03920683.</p>