Background: Nasolacrimal duct (NLD) obstruction and tear film abnormalities occur frequently in children with trisomy 21. This study describes the outcomes of treatment for NLD obstruction in this population. Methods: The records of 15 children with trisomy 21 treated for NLD obstruction were reviewed. Eight patients were initially treated with NLD probing with or without placement of nonfixated lacrimal stents. Because of poor success with this procedure, the initial treatment of children with trisomy 21 and NLD obstruction was changed to balloon catheter dilation in 1997. Outcomes were considered excellent if the patient had complete resolution of epiphora and dacryocystitis, good if the patient had only mild residual symptoms, fair if the patient had significant residual symptoms, and poor if there was no improvement. Results: Of 8 patients treated initially with NLD probing, 5 had fair or poor outcomes. These patients all had good outcomes after placement of nasally fixated lacrimal stents, balloon catheter dilation, or both. Of 7 patients treated initially with balloon catheter dilation, 5 had excellent or good outcomes and 2 had fair or poor outcomes. Conclusion: Simple NLD probing is often unsuccessful in treating NLD obstruction in children with trisomy 21. Balloon catheter dilation appears to be a reasonable alternative first treatment in these patients.