Introduction: Acromegaly is characterized by a very particular alteration of bone microarchitecture, leading to increased vertebral fragility. However, due to inconsistent and insufficient evidence, no guidelines are available for the evaluation of this osteopathy. Methods: We performed a literature review of studies published between 1968 and January 2022 on the PubMed and SCOPUS databases using the terms “acromegaly” and “vertebral fractures”. Twenty-four studies were found eligible for inclusion, published between June 2005 and November 2021. Included studies evaluated acromegaly patients, who were assessed for the presence of vertebral fractures. We excluded case reports, reviews, meta-analyses, letters to the editor, articles not written in English, and research performed on the same set of patients without significant differences in study design. Risk of bias was avoided by following the ROBIS risk of bias recommendations. We executed rigorous data collection, and the results are depicted as a narrative overview, but also, as statistical synthesis. Limitations of the evidence presented in the study include study heterogeneity, small sample sizes, and a small number of prospective studies with short follow-up. Findings: Data regarding vertebral fractures (VFs) in acromegaly and their influencing factors are variable. Twenty-four studies were included, nine out of which had a prospective design. The smallest group of acromegaly patients had 18 subjects and the largest included 248 patients. Prevalence ranges between 6.5% and 87.1%, although most studies agree that it is significantly higher than in controls. VFs also have a higher incidence (between 5.6% and 42%) and are more frequently multiple (between 46.15% and 71%). Evidence shows that disease activity and active disease duration are influencing factors for the prevalence and incidence of VFs. Nonetheless, hypogonadism does not seem to influence the frequency of VFs. While reports are conflicting regarding the use of bone mineral density in acromegaly, evidence seems to be slightly in favor of it not being associated with VFs. However, trabecular bone score is significantly lower in fractured patients, although no prospective studies are available. Interpretation: Vertebral fractures evaluation should be performed with regularity in all acromegalic patients, especially in the presence of active disease. Disease activity is an important determinant of vertebral fracture incidence and prevalence, although hypogonadism is less so. To clarify the predictive value of both BMD and TBS for vertebral fractures, additional, larger, prospective studies are necessary.