© TÜBİTAK.Background/aim: The known pathogenesis of diabetes mellitus (DM) in acromegaly is mainly based on growth hormone (GH) and insulin-like growth factor-1 (IGF-1) excess. Fatty acid-binding protein 4 (FABP-4), a novel adipokine, is found to induce insulin resistance and type 2 DM. We aimed to investigate the possible effect of FABP-4 on glucose metabolism in patients with acromegaly. Materials and methods: This case-control study included 28 patients newly diagnosed with acromegaly and 57 healthy volunteers. The patients with acromegaly were classified according to their glycemic status as with DM, prediabetes, and normal glucose tolerance. Anthropometric measurements, laboratory test results, and FABP-4 levels of the subjects were evaluated. Results: Although no difference was observed in FABP-4 levels between acromegaly and control groups, the FABP-4 level was higher in the patients with acromegaly having DM compared to the patients with acromegaly having prediabetes and NGT, and the control group (p = 0.004, p = 0.001, p = 0.004, respectively). Logistic regression analysis suggested that the FABP-4 is an independent predictor of DM in acromegaly (β = 7.382, OR = 38.96, 95% CI: 1.52-5.76, p = 0.018). Conclusion: The FABP-4 may be a helpful predictor of acromegaly-associated DM.