<b><i>Introduction:</i></b> Acromegaly is commonly complicated by arthropathy and skeletal fragility with high risk of vertebral fractures (VFs). <b><i>Objective:</i></b> This study aimed to assess whether VFs may be associated with sagittal spine deformities, arthropathy, impaired quality of life (QoL), pain, and disability. <b><i>Methods:</i></b> Thirty-eight patients with acromegaly (median age: 55 years, 20 males) and 38 matched control subjects were evaluated by a low-dose sagittal and coronal planes, X-ray imaging system (EOS®-2D/3D) for morphometric VFs, radiological signs of spine arthropathy, and spine deformities (Cobb thoracic index ≥40°, pelvic incidence minus lumbar lordosis ≥10°, pelvic tilt &#x3e;20°, and sagittal vertical axis ≥4 cm) determining sagittal spine imbalance. Acromegalic patients were also evaluated by questionnaires for QoL (Acromegaly QoL Questionnaire [AcroQoL] and Short Form-36 [SF-36]) and pain and disability (Western Ontario and McMaster University [WOMAC]). <b><i>Results:</i></b> Acromegalic patients showed higher prevalence of thoracic hyperkyphosis (i.e., Cobb thoracic index ≥40°; <i>p</i> = 0.04) and pelvic tilt &#x3e;20° (<i>p</i> = 0.02) than control subjects. VFs were found in 34.2% of acromegalic patients (<i>p</i> = 0.003 vs. control subjects), in relationship with higher prevalence of hyperkyphosis (<i>p</i> = 0.03), pelvic tilt &#x3e;20° (<i>p</i> = 0.04), sagittal vertical axis ≥4 cm (<i>p</i> = 0.03), and moderate/severe subchondral degeneration (<i>p</i> = 0.01). Moreover, patients with VFs had lower AcroQoL general health (<i>p</i> = 0.007) and SF-36 general health (<i>p</i> = 0.002) scores and higher WOMAC pain (<i>p</i> = 0.003) and global (<i>p</i> = 0.009) scores than patients who did not fracture. <b><i>Conclusions:</i></b> In acromegaly, VFs may be associated with spine deformities and sagittal imbalance, spine arthropathy, impaired QoL, and disability.