AIM: To compare safety and efficacy of intravitreal dexamethasone (IVD) implant with topical nepafenac (TN) 0.1% in previously untreated Irvine-Gass syndrome (IGS) in clinical practice. METHODS: This was a retrospective study of 62 eyes with IGS after phacoemulsification with posterior chamber intraocular lens (IOL) implantation. None of the patients used treatment before IVD or TN. Best-corrected visual acuity (BCVA) with Early Treatment Diabetic Retinopathy Study chart (ETDRS), slit-lamp, intraocular pressure (IOP) measurement, fundus examination, spectral-domain optical coherence tomography (OCT) and fundus florescein angiography were performed to all subjects at baseline, 1, 3 and 6mo. RESULTS: The mean BCVA of the IVD group was 49.3±6.8, and the mean BCVA of the TN group was 32.9±7.3 ETDRS letters in post-treatment month 6. The mean central macular thickness (CRT) of IVD group was 266.6±53.5 µm and the mean CRT of TN group was 364.9±56.3 µm in post-treatment month 6. Baseline BCVA has correlation with final BCVA in TN group however there was no correlation between baseline BCVA and final BCVA in IVD group. CONCLUSION: IVD is found to be better than TN in controlling pseudophakic macular edema and improving visual acuity. IVD group also has significantly lower CRT however IOP is not significantly different between two groups in post-treatment month 6.