Purpose: To investigate the relationship between early post-operative anterior chamber inflammation (aqueous flare) and central corneal thickness (CCT) after cataract surgery and to evaluate the effect of anti-inflammatory prophylaxis on CCT. Setting: Department of Ophthalmology, Rigshospitalet-Glostrup, University Hospital Copenhagen, Denmark. Design: Post-hoc analysis of a prospective randomized controlled trial. Patients and Methods: A total of 470 participants who underwent standard cataract surgery were randomly allocated to prophylactic treatment with nonsteroidal anti-inflammatory drug (NSAID, groups C and D) or a combination of NSAID and steroid eye drops (groups A and B), commenced either pre-operatively (A and C) or post-operatively on the day of surgery (B and D), or “drop-less surgery” (peri-operative subtenon depot of dexamethasone, group E). Aqueous flare was measured before and three days after surgery. CCT was measured before surgery, three days, three weeks, and three months after surgery. Data were analyzed according to the intention-to-treat method. Results: Doubling of aqueous flare increased mean CCT by 15.6 microns (95% CI 9.8; 21.3, P<0.001) three days after surgery. Mean CCT increased from 549 microns (95% CI 545; 552) at baseline to 594 microns (95% CI 585; 602) three days after surgery and returned to 551 microns (95% CI 545; 557) three months after surgery. Mean CCT was thinner in group C compared to group A three days after surgery. No difference was found for any other groups or time points. Conclusion: Increased anterior chamber inflammation was associated with significant corneal thickening three days after cataract surgery. Choice of anti-inflammatory regimen seemed to be of no or minimal importance on CCT when the effect of inflammation was accounted for. Corneal thickening is possibly mediated by underlying deterioration of the blood-aqueous barrier and corneal endothelium pump function caused by a post-operative inflammatory response.