AIM: To evaluate the safety and efficacy profile of 27-gauge (27G) pars plana vitrectomy (PPV) for the treatment of various vitreoretinal diseases. METHODS: The clinical outcomes of 61 eyes (58 patients) with various vitreoretinal diseases following 27G PPV were retrospectively reviewed. RESULTS: Surgical indications included rhegmatogenous retinal detachment (n=24), full-thickness macular hole (n=12), diabetic retinopathy (n=11), vitreous hemorrhage (n=6), Eales disease (n=4), pathological myopia-related vitreous floater (n=2), and macular epiretinal membrane (n=2). The mean follow-up was 166.4±61.3d (range 98-339d). The mean logMAR best-corrected visual acuity (BCVA) improved from 1.7±1.1 [0.02 decimal visual acuity (VA) equivalent] preoperatively to 1.2±1.0 (0.06 decimal VA equivalent) at the last postoperative visit (P<0.001). The mean operative time was 49.9min. With the exception of complicated cataract in one eye, no intraoperative complications were encountered. No case required conversion to conventional 20-, 23- or 25G instrumentation in all surgical maneuvers except for silicone oil infusion, which required a 25G oil injection syringe. Postoperative complications included transient ocular hypertension, vitreous hemorrhage, persistent intraocular pressure elevation, subconjunctival oil leakage, and recurrent retinal detachment. No cases of hypotony, endophthalmitis, and sclerotomy-related tears were observed. CONCLUSION: The current results suggest that 27G PPV system is a safe and effective treatment for various vitreoretinal diseases. When learning to perform 27G PPV, surgeons may encounter a learning curve and should gradually expand surgical indications from easy to pathologically complicated cases.