Purpose: To compare the short term effects of preserved prednisolone acetate to preserved nepafenac eye drops on punctal size and tear film. Methods: 50 eyes of 48 patients who were scheduled for cataract surgery were randomized to either prednisolone acetate or nepafenac eye drops (both preserved with 0.005% benzalkonium chloride) for the first 3 weeks of the post-operative period. Punctal size and tear meniscus were measured via AS-OCT once pre-operative, then at 2 weeks, 1 month and 3 months post-operative. Punctal size was measured on AS-OCT as punctal outer, inner diameters and height. Tear meniscus was measured on AS-OCT as tear meniscus height and area. Results: No statistically significant differences were observed regarding punctal size between the 3 months post-operative visit and the pre-operative (predisolone group: p-value: 0.987, 0.795 and 0.140 for outer, inner diameters and height respectively) (nepafenac group: p-value: 0.236, 0.183, 0.661 for outer, inner diameters and height respectively). Moreover, comparison of both groups to each other revealed no statistically significant differences (p-value: 0.330, 0.432, 0.205 for outer, inner diameters and height respectively). Statistically significant increase in tear meniscus height (prednisolone: p-value = 0.046, nepafenac: p-value = 0.001) and tear meniscus area (prednisolone: p-value = 0.019, nepafenac: p-value = 0.001) was noted after 2 weeks of topical treatment. Conclusions: Short term preserved prednisolone acetate and nepafenac eye drops have no effect on the lacrimal punctal size. Benzalkonium chloride has a short term effect on tear film stability observed as increased tear meniscus parameters on AS-OCT.