Following previous reports of pupil size decrease after femtosecond treatment, the authors compare levels of prostaglandins in patients undergoing femtosecond assisted cataract surgery with those having routine cataract surgery. Patients with inflammatory eye disease, previous trauma surgery, age-related macular degeneration (AMD), retinopathy, glaucoma, non-steroidal anti-inflammatory (NSAID) use and small pupils were excluded. Aqueous humour was collected from patients after femtosecond laser pretreatment (n=113) and at the beginning of routine cataract surgery (n=107). In all femtosecond assisted cases, a set capsulotomy size was used and the programmed pulse energy, incision depth and grid spacing were standardised. The total prostaglandin (PG) and the prostaglandin E2 (PGE2) concentrations were measured in two independent studies each using an enzyme-linked immunoassay. In both sets of studies, there was a significantly higher concentration of PG (p=0.0001, p=0.00004) and PGE2 (p=0.0002, p=0.004) in the femtosecond group compared to routine cataract surgery group. No correlation of PG/PGE2 levels with age, cataract density, corneal incision type, suction time or laser time was noted. The authors therefore postulate that the possible trigger for prostaglandin release is from the microplasma of gas and water that results from the laser application. They suggest that patients undergoing femtosecond assisted cataract surgery should be pretreated with topical NSAIDs to avoid intraoperative mioses and postoperative inflammation.