PURPOSE: To report a case of recalcitrant epithelial ingrowth after small incision lenticule extraction (SMILE) treated successfully with a novel hydrogel ocular sealant. METHODS: Case report and literature review. RESULTS: A 32-year-old man who underwent small incision lenticule extraction (SMILE) complicated by difficult lenticule extraction developed visually significant epithelial ingrowth. He then underwent two flap lifts and epithelial scrapings and flap edge suturing with recurrence of epithelial ingrowth despite these interventions. He subsequently underwent repeat scraping, followed by hydrogel ocular sealant placement (ReSure Sealant; Ocular Therapeutix, Inc., Bedford, MA), which prevented recurrence of epithelial ingrowth and reduced corneal haze. The patient was also found to have undiagnosed diabetes, suggesting that just as in LASIK, diabetes may be a risk factor for epithelial ingrowth after SMILE. CONCLUSIONS: Interface epithelial ingrowth is a potential complication after SMILE and diabetes may be a risk factor for this complication. Hydrogel ocular sealant may be effective after SMILE to prevent epithelial ingrowth into the interface.