Recurrent corneal erosion syndrome is a debilitating condition for which there are many treatment options with varying rates of success. One treatment of interest in recent years is the combination of oral doxycycline and topical corticosteroids, both of which have been shown to inhibit key metalloproteinases important to disease pathogenesis. To assess the efficacy of this treatment, we conducted a retrospective single-observer case series involving all patients with recurrent corneal erosion syndrome who were treated at a community-based clinic with oral doxycycline and topical corticosteroid between January 2000 and July 2007. Twenty-one patients were identified. All received oral doxycycline 50 mg twice daily and topical fluoromethalone 0.1% three times daily for at least 4 weeks. At 8 weeks post commencement of treatment, 15/21 patients (71%) were symptom free. All but one of these patients reported an improvement in symptoms. Of those patients not lost to follow up, 15/18 patients (83%) and 11/15 patients (73%) denied any symptoms suggestive of relapse at 6 and 12 months, respectively. Among the patients in remission was one who had responded poorly to other treatments including ocular lubricants, epithelial debridement, serum eyedrops, anterior stromal puncture, and phototherapeutic keratectomy. Treatment of recurrent corneal erosion syndrome with the combination of oral doxycycline and topical corticosteroid is effective. It may help patients with recurrent corneal erosion syndrome who have failed other forms of treatment. This non-invasive treatment modality should also be considered as the first treatment option when conservative management with ocular lubricants fails.