Background and aims: The individual risk of developing diabetes-related complications (DRC) is extremely variable in T2D and an overlap between macro (MVC) and microvascular (µVC) complications exists. We developed a score to measure the overall burden of DRC including 3 main MVC (coronary, lower limbs, cerebrovascular) and 4 main µVC (eye, nerves, kidney, foot). Methods: This multicenter retrospective study evaluated T2D patients who regularly attended 4 different diabetes clinics (≥3 visits in the previous 3 years) in Italy or Greece. Data on MVC and µVC were retrieved from the electronic medical records, and scored either 0, 1 or 3 if absent, subclinical (instrumentally detected) or overt (clinically manifest), respectively. Results: 1,302 subjects (age 69±13 years, 37% women, disease duration 14±16 years) were included in the final analysis. Among them, 1,170 (90%) subjects had DRC score ≥1; as compared with patients with DRC score <1, they were older (70±12 vs 62±15.5 years, p<0.0001) and with longer disease (8±12 vs 4±8 years, p<0.0001). Subclinical MVC and µVC occurred in 831 (64%) and 980 (75%) patients, while overt disease was present in 390 (30%) and 473 (36%) patients, respectively. The presence of overt µVC increased the likelihood to have overt MVC (OR 2.5 [2.0-3.2], p<0.0001). The median DRC score was 3±5 points, being higher in men (p<0.0001), increasing with age (R2=0.06, p<0.0001), and with diabetes duration (r2 0.14, p<0.0001) with an intercept of -17 years. The individual ratio of DRC score and disease duration was used to calculate susceptibility to DRC, and the 2 extreme quintiles of this distribution identified subjects extremely resistant (DRC score=0.04+0.3/10yrs) and extremely susceptible to DRC (DRC score=6.11+2/10 years). Conclusions: Our findings confirm the large interindividual variability in developing DRC, which is only partially explained by diabetes duration and the clustering of MVC and µVC. We also demonstrate that by evaluating the DRC score in relation with disease duration, it is possible to measure the individual susceptibility to DRC, which could help clinicians in deciding the intensity of both complications screening and risk factors’ management.