Key PointsQuestionWhat are the biochemical changes associated with ambroxol repurposing among patients with Gaucher disease who have not received any disease-specific treatment?FindingsIn this case series of 28 unselected participants, significant improvements in hematologic parameters, visceral volumes, and plasma biomarkers were observed for 26 patients after a mean (SD) treatment duration of 2.6 (1.7) years.MeaningLong-term treatment with ambroxol was associated with patient improvement; improvements in hematologic parameters, visceral volumes, and plasma biomarkers were larger among patients with relatively mild symptoms of Gaucher disease and patients who received initial treatment at younger ages.