PURPOSE: To compare the incidence of laser in situ keratomileusis (LASIK)-associated dry eye and the need for postoperative cyclosporine A treatment after flap creation with a femtosecond laser and a mechanical microkeratome. SETTING: Cole Eye Institute, Cleveland, Ohio, USA. METHODS: Eyes were randomized to flap creation with an IntraLase femtosecond laser (30 or 60 kHz) or a Hansatome microkeratome. No patient had signs, symptoms, or treatment of dry eye preoperatively. Flap thickness was determined by intraoperative ultrasonic pachymetry. Slitlamp assessments of the cornea and need for postoperative dry-eye treatment were evaluated preoperatively and 1 month postoperatively. RESULTS: The flap was created with the femtosecond laser in 113 eyes and with the microkeratome in 70 eyes. The difference in mean central flap thickness between the femtosecond group (111 mum +/- 14 [SD]) and the microkeratome group (131 +/- 25 mum) was statistically significant (P<.001). The incidence of LASIK-associated dry eye was statistically significantly higher in the microkeratome group (46%) than in the femtosecond group (8%) (P<.0001), as was the need for postoperative cyclosporine A treatment (24% and 7%, respectively) (P<.01). In the microkeratome group, there was no correlation between thick flaps and a higher incidence of LASIK-induced dry eye. CONCLUSIONS: Eyes with femtosecond flaps had a lower incidence of LASIK-associated dry eye and required less treatment for the disorder. In addition to neurotrophic effects from corneal nerve cutting, other factors may be important because no correlation was found between flap thickness (or ablation depth) and the incidence of LASIK-induced dry eye.