For a study, researchers sought to look into the factors contributing to biopsychosocial complexity in a group of acromegaly patients with varying disease activity. An observational cross-sectional study was carried out. First, a linguistic adaptation of the INTERMED – self-assessment questionnaire (IMSA) was developed, followed by an assessment of biopsychosocial complexity among patients with acromegaly and the factors associated with complexity. To evaluate, the following tools were used: The INTERMED – self-assessment (IMSA) measures biopsychosocial complexity; the World Health Organization Quality of Life – BREF (WHOQoL) and the Acromegaly Quality of Life questionnaire (AcroQol) measures the quality of life; and the General Health Questionnaire – 28 measures mental state (GHQ-28). A total of 71 patients were included in the final analysis. According to the principal component analysis, the most important factors related to clinical complexity in patients with acromegaly were mental state (GHQ-28) and quality of life (AcroQol). Higher growth hormone (GH) concentration, longer illness duration, and better general quality of life were included as clinical complexity protective factors in the model created by stepwise regression analysis for the total IMSA score. A high score on the GHQ-28’s severe depression subscale, on the other hand, was associated with greater clinical complexity. In the group of patients with acromegaly, the most important determinants of clinical complexity were mental state and quality of life, while biochemical normalization was less important.