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Prevention of postoperative endophthalmitis (POE) is a goal of every ophthalmic procedure and also in intravitreal therapy (IVT). This comparative retrospective study targets whether systemic and topical preoperative antibiotic prophylaxis (PAP) regimen does prevent POE after IVT in a higher rate compared with topical PAP alone. Out of 6111 IVT performed over a period of 103.5 months, in the study group A patients were treated with systemic and topical PAP (2881 IVT), and in the study group B patients were treated only with topical PAP (3230 IVT). Intravitreal drugs were anti-VEGF, triamcinolone and dexamethasone implants. The incidence of POE in group A (1/2881 or 0.035 % per injection) was not significantly different ( P = 0.4) from that in suite B (1/3230 or 0.031 % per injection). Our study states that systemic PAP does not modify the risk of postoperative endophthalmitis in patients treated with IVT. [ABSTRACT FROM AUTHOR]