Although GH and IGF-1 excess has a controversial impact on bone mineral density (BMD), acromegalic patients display variable degrees of bone structure impairment. In this study, we aim to investigate the usefulness of trabecular bone score (TBS), compared to BMD, in identifying acromegalic patients with impaired lumbar spine trabecular microarchitecture. Forty-four acromegalic patients were investigated for disease control, metabolic and gonadal status, bone metabolism parameters, and the presence of vertebral fractures (VFs). Patients and matched healthy controls underwent BMD and TBS examination. Mean TBS values were lower in patients than in controls (p < 0.001), without significant differences in mean lumbar and femoral BMD. TBS values were significantly higher in controlled patients compared to the uncontrolled ones (p = 0.012). No significant differences were found in bone markers with respect to disease control. Mean TBS or lumbar BMD did not significantly differ in patients with or without VFs (prevalence 11.4%). TBS and BMD levels were lower in hypogonadal patients compared to the eugonadal ones (p = 0.030 and p < 0.001, respectively). In conclusion, TBS values are significantly lower in patients than in controls, confirming the presence of impaired lumbar spine trabecular bone in acromegaly. Both uncontrolled disease and hypogonadism contribute to TBS deterioration in acromegaly.