Based on the indications, one-third to one-half of patients can achieve full-thickness macular hole (FTMH) closure with or without the separation of vitreomacular adhesion (VMA) within 28 days of ocriplasmin treatment. The authors report the case of a 63-year-old man with early VMA separation and delayed FTMH closure after ocriplasmin treatment. Four weeks posttreatment, the posterior vitreous detachment occurred at the optic disk, and the macular hole (MH) started decreasing thereafter. MH closure was finally achieved at 10 weeks posttreatment, leaving minimal subretinal fluid. The patient's vision improved from 0.8 LogMAR (pretreatment) to 0.3 LogMAR (12 weeks posttreatment). This case suggests that FTMH closure can be achieved within 28 days of ocriplasmin treatment.