AIM: To compare pain level and inflammation between preoperative topical Diclofenac 0.1% and Nepafenac 0.1% in patients undergoing cataract surgery. METHODS: This research was designed as prospective randomized clinical trial and conducted in June to August 2017 at Dr. Yap Eye Hospital. There were 56 subjects underwent phacoemulsification operation (single operator) and diagnosed as senile cataract and no adverse events were found. Subjects were divided into 2 groups according to preoperative eye drop medication, namely Diclofenac group and Nepafenac group. Participants and phaco-surgeon were blind regarding to the treatment. Inflammation parameters (at 1, 7 and 14d follow up) such as pain, conjunctiva hyperemic, blepharospasm, flare and cell in anterior chamber level as the primary outcome, whereas density and morphology of corneal endothelial cells as the secondary outcome. RESULTS: There were no statistically difference in conjunctiva hyperemic and blepharospasm level between 2 groups at 1d (P=0.284, effect size=0.29, 95%CI=-0.09 to 0.31; P=0.254, effect size=0.31, 95%CI=-0.13 to 0.49, respectively) and 7d (P=1.000 and P=0.556, effect size=0.18, 95%CI=-0.08 to 0.16, respectively) postoperatively. The pain scores (during surgery, 1d and 14d postoperative) in Nepafenac group was statistically lower than Diclofenac group (P=0.006, effect size=0.77, 95%CI=0.24 to 1.34; P=0.045, effect size=0.39, 95%CI=-0.10 to 0.62; and P=0.014, effect size=0.69, 95%CI=-0.06 to 0.50, respectively). The degree of flare and cell in Nepafenac group was lower at the 1d after phacoemulsification (P=0.029, effect size=0.59, 95%CI=0.02 to 0.36). Reduction of corneal endothelial density between 2 groups was not statistically significant, however the reduction of hexagonal cell percentage at 7d after phacoemulsification was lower than Nepafenac group (P=0.042, effect size=-0.55, 95%CI=-2.33 to -0.03). CONCLUSION: The pain and flare-cell levels in Nepafenac group are lower when compared with Diclofenac group.