Gaucher disease (GD) is a genetic lysosomal disorder characterized by high bone marrow (BM) involvement and skeletal complications. The pathophysiology of these complications is not fully elucidated. Magnetic resonance imaging (MRI) is the gold standard to evaluate BM. This study aimed to apply machine-learning techniques in a cohort of Spanish GD patients by a structured bone marrow MRI reporting model at diagnosis and follow-up to predict the evolution of the bone disease. In total, 441 digitalized MRI studies from 131 patients (M: 69, F:62) were reevaluated by a blinded expert radiologist who applied a structured report template. The studies were classified into categories carried out at different stages as follows: A: baseline; B: between 1 and 4 y of follow-up; C: between 5 and 9 y; and D: after 10 years of follow-up. Demographics, genetics, biomarkers, clinical data, and cumulative years of therapy were included in the model. At the baseline study, the mean age was 37.3 years (1–80), and the median Spanish MRI score (S-MRI) was 8.40 (male patients: 9.10 vs. female patients: 7.71) (p< 0.001). BM clearance was faster and deeper in women during follow-up. Genotypes that do not include the c.1226A>G variant have a higher degree of infiltration and complications (p= 0.017). A random forest machine-learning model identified that BM infiltration degree, age at the start of therapy, and femur infiltration were the most important factors to predict the risk and severity of the bone disease. In conclusion, a structured bone marrow MRI reporting in GD is useful to standardize the collected data and facilitate clinical management and academic collaboration. Artificial intelligence methods applied to these studies can help to predict bone disease complications.