Context: There is no uniform standard of care for acromegaly. Due to the high costs involved, steps must be taken to ensure the cost-effective delivery of treatment., Objective: Taking the results of an earlier meta-analysis as a starting point, this study aims to determine whether treatment with long-acting somatostatin analogue (SSA) prior to surgery improves the cost-effectiveness of the treatment of acromegaly., Methods: The results are presented as an Incremental Cost Effectiveness Ratio (ICER) immediately after surgery, for the following year and over the next four decades. The cure rates percentage (95% CI) for the three randomized prospective controlled trials were 44.4% (34.2-54.7) and 18.2% (10.1-26.3) for preoperative treated and untreated patients respectively. The cost of pharmacological treatments was based on the number of units prescribed, dose and length of treatment., Results: The mean (95% CI) ICER immediately after surgery was €17,548 (12,007-33,250). In terms of the postoperative SSA treatment, the ICER changes from positive to negative before two years after surgery. One decade after surgery the ICER per patient/year was €-9973 (-18,798; -6752) for postoperative SSA treatment and €-31,733 (-59,812; -21,483) in the case of postoperative pegvisomant treatment., Conclusions: In centres without optimal surgical results, preoperative treatment of GH-secreting pituitary macroadenomas with SSA not only shows a significant improvement in the surgical results, but is also highly cost-effective, with an ICER per patient/year one decade after surgery, of between €-9973 (-18,798; -6752) and €-31,733 (-59,812; -21,483) for SSA and pegvisomant respectively., (Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)