Abstract Purpose We aimed to evaluate the risk of psychiatric disorders through a retrospective cohort study comparing acromegaly and non-functioning pituitary adenomas (NFPAs) and a meta-analysis of existing literature. Methods The cohort study included data from patient records analyzed using Chi2-, T-tests and binary regression. The meta-analysis included studies retrieved from PubMed, Embase and PsycINFO that reported risk of psychopathology in acromegaly compared to NFPA or healthy controls, using a random effects model. Results The study population comprised 105 acromegaly and 211 NFPA patients, with similar sex distributions. Patients with acromegaly presented with smaller pituitary adenomas (17.9 (SD: 9.9) mm vs. 22.9 (SD: 10.6) mm, p < 0.001), more frequent pituitary surgery (89.1 vs. 60.2%, p < 0.001) and hormone replacement therapy (25.7 vs. 16.1%, p = 0.042). Acromegaly patients had higher risk of depression (RR: 1.9, CI95% [1.2–3.2], p = 0.009), and increased need of admissions to the psychiatric ward (5.7 vs. 0.5%, p = 0.006). The relative risk of anxiety was 1.4 (CI95% [0.5–4.4], p = 0.53). Daily opioid use was higher in acromegaly patients with psychiatric morbidity which was associated with a diagnosis of arthropathy (p = 0.009). From the meta-analysis (8 studies, 1387 patients) an increased risk of depression (RR:1.8, CI95% [1.3–2.5]) and anxiety (RR:1.9, CI95% [1.1–3.2]) was observed in acromegaly compared to NFPAs. Conclusion This study reveals a higher risk of psychiatric disorders in acromegaly, particularly depression and anxiety. Consequently, a need for increased psychiatric awareness in acromegaly is warranted.