This study was performed to investigate the therapeutic effect of umbilical cord serum eyedrops on dry eye associated with graft-versus-host disease (GVHD). Twenty-four eyes of 12 patients with severe dry eye syndrome associated with GVHD were treated with 20% umbilical cord serum eyedrops. Symptom scoring, corneal sensitivity test, tear film break up time (BUT), Schirmer test, tear clearance rate (TCR), and corneal fluorescein staining were performed before and 2 and 6 months after treatment. Six months after treatment, significant improvement was observed in symptom score (from 3.83+/-0.38 to 0.83+/-0.57, P<0.01), corneal sensitivity (from 52.08+/-6.06 mm to 57.50+/-3.00 mm, P<0.01), tear film BUT (from 2.50+/-0.91 s to 5.71+/-1.04 s, P<0.01), and keratoepitheliopathy score (from 7.42+/-2.02 to 1.29+/-0.46, P<0.01). There was no siginificant change in Schirmer test and TCR results. No significant complications associated with the use of the eyedrops were observed. Umbilical cord serum eyedrops are safe and may be an effective way to treat severe dry eye associated with GVHD.