Abstract Background: A prospective observational study was conducted with the purpose of evaluating the role of autologous platelet-rich plasma (PRP) in the form of a clot as an adjunct in surgery for the closure of large full-thickness macular holes (>400 μm). Methodology: Thirteen patients with a diagnosis of full-thickness macular hole larger than 400 μm, without associated pathologies or previous vitreoretinal surgeries, were selected. Each patient underwent a complete ophthalmological evaluation, including visual acuity (uncorrected or best corrected), optical coherence tomography (OCT Optovue), and in some cases, retinal photographs. On the day of the procedure, blood samples were taken to prepare PRP and form a clot according to institutional protocol. Patients were followed for 1 year with periodic evaluations that included OCT, retinal photographs, and assessments by a retina specialist and optometry. Results: Of the 13 patients, 46% (6 cases) had an epiretinal membrane as the triggering factor for the macular hole and 54% (7 cases) had vitreomacular traction. Complete closure of the macular hole was achieved in 92.31% (12 cases) and partial closure in 7.69% (1 case). Postoperative best-corrected visual acuity ranged from 20/30 to 20/200 according to the Snellen chart. No patient experienced a deterioration in visual acuity after the procedure. Conclusions: The use of PRP as an adjunct treatment for macular hole surgery in patients without previous vitreoretinal surgeries has proven to be effective in achieving complete or partial closure in a high percentage of cases. Pre-and postoperative changes in visual acuity, hole size, and type of closure provide valuable information on the efficacy of PRP treatment in these patients.