CONTEXT: Secondary diabetes mellitus occurs in 30-50% of patients with acromegaly despite a lean phenotype, whereas type 2 diabetes mellitus (T2DM) is associated with adiposity. OBJECTIVE: We compared mortality, morbidity and treatment patterns between patients with acromegaly-associated diabetes (ACRO-DM) and T2DM. DESIGN: Nationwide, retrospective, matched-cohort study in Sweden. METHODS: The ACRO-DM group included patients with an acromegaly diagnosis in the Patient Register, with diabetes registered in the National Diabetes Register (NDR) or a dispensed glucose-lowering drug in the Prescribed Drug Register. Controls with T2DM from the NDR were matched 10:1 for sex, age, calendar year, diabetes duration. We derived mortality and morbidity outcomes from the Death and Patient Registers. RESULTS: We included 348 patients with ACRO-DM and 3,480 with T2DM. Mean (SD) age was 60.3 (13.2) and 59.5 (15.6) years while diabetes duration was 2.8 (5.8) and 3.0 (7.1) years in ACRO-DM and T2DM, respectively. Baseline cardiovascular morbidity was more common in ACRO-DM than T2DM group (61% vs 43%), including hypertension (48% vs 29%), heart failure (11% vs 5%), arrhythmia (13% vs 9%) and stroke (8% vs 5%).The hazard ratio (HR) for overall mortality was 1.18 (95% CI, 0.96-1.46) in ACRO-DM compared with T2DM group. The ACRO-DM group had a higher risk of cardiovascular morbidity (HR 1.55; 95% CI, 1.24-1.94), with increased hazards for venous thromboembolism, specifically pulmonary, and arrhythmia, whereas cardiovascular mortality was not increased (HR 1.12; 95% CI, 0.78-1.60). CONCLUSIONS: The risk of cardiovascular morbidity was increased in patients with ACRO-DM compared to T2DM.