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Introduction: An increased risk of mortality in patients with uncontrolled acromegaly has been reported in several studies. We aimed to assess the impact of co-morbidities on the survival of patients with acromegaly after long-term treatment and follow-up., Material and Methods: A retrospective analysis was performed for 285 patients with active acromegaly, who were admitted to the Chang Gung Memorial Hospital, Taiwan between 1978 and 2012. Of these patients, 106 (37.2%) were diagnosed with diabetes mellitus (DM). During the follow-up period, 21 cases of histological proved malignant in acromegalic patients, and DM with acromegaly had a higher incidence of malignancy (13.2% vs. 3.8%; p < 0.01). The 5-, 10-, and 20-year survival rates were 93.1%, 86.9%, and 84.7% for the DM group, respectively, and 96.5%, 96.5%, and 96.5% for the non-DM group, respectively. After a mean follow-up of 15.1 ± 0.6 years, age, DM, coronary heart disease, and malignancy were found to be significant factors of mortality. Control of growth hormone and IGF-1 levels also conferred a marginal survival benefit., Conclusions: DM and malignancy significantly influence the survival of patients with acromegaly; thus, these patients need close follow-up and appropriate therapy. (Endokrynol Pol 2016; 67 (5): 501-506).