Aims: To identify early clinical predictors of depressive syndrome in people with Type 2 diabetes. Methods: Depressive syndrome was assessed in 325 individuals with Type 2 diabetes 15 years after a baseline assessment, which included information on antidepressant use and depressive symptoms obtained using a quality-of-life scale. Follow-up current and lifetime depressive syndrome were assessed using the nine-item Patient Health Questionnaire and the Brief Lifetime Depression Scale and taking account of antidepressant use. Analyses were conducted inclusive and exclusive of antidepressant use where Patient Health Questionnaire criteria were not met. Results: At baseline, the participants were aged 57.2±9.3 years and the median (interquartile range) diabetes duration was 2.2 (0.6–6.0) years. After a mean of 14.7±1.1 years’ follow-up, 81 participants (24.9%) had depressive syndrome (14.8% defined by the Patient Health Questionnaire, 10.2% defined by antidepressants) and 31.4% reported lifetime depression, and in 10.2% of participants this preceded diabetes onset. With logistic regression (inclusive of antidepressants), follow-up depressive syndrome was negatively associated with education level [odds ratio 0.39 (95% CI 0.20–0.75)] and antidepressant use [odds ratio 0.11 (95% CI 0.03–0.36)] and was positively associated with depression history before diabetes onset [odds ratio 2.79 (95% CI 1.24–6.27)]. In the model exclusive of antidepressants, depressive syndrome was positively associated with baseline depressive symptoms [odds ratio 2.57 (95% CI 1.32–5.03)] and antidepressant use [odds ratio 3.54 (95% CI 1.20–10.42)] and was negatively associated with education level [odds ratio 0.39 (95% CI 0.19–0.81)]. Conclusions: Risk factors for depressive syndrome can be identified early after the onset of Type 2 diabetes. The early presence of depressive symptoms or its treatment and/or history of depression are likely indicators of vulnerability. Early risk stratification for late depressive syndrome is feasible in people with Type 2 diabetes and could assist with depression treatment or prevention.