Purpose: To analyze the incidence of diffuse lamellar keratitis (DLK) after laser in situ keratomileusis (LASIK) performed with an IntraLase 15 kHz femtosecond laser (IntraLase, Corp.) or a Moria M2 mechanical microkeratome (Moria SA). Setting: Vissum Madrid, Madrid, Spain. Methods: This retrospective study compared the incidence of DLK in consecutive LASIK procedures performed with the IntraLase 15 kHz femtosecond laser (study group) or the Moria M2 microkeratome (control group). Two surgeons performed both types of surgeries (femtosecond laser and microkeratome) using the same excimer laser (Technolas 217, Bausch & Lomb). During the first week postoperatively, topical dexamethasone drops were applied 8 times daily in the femtosecond group and 4 times daily in the mechanical microkeratome group. Results: A total of 2000 consecutive eyes were analyzed (1000 eyes in each group). Diffuse lamellar keratitis stage 2 developed in 1 patient in each group; DLK stage 3 developed in 4 patients in the study group and in no patient in the control group (P = .03). Conclusion: Despite more intense postoperative steroid treatment, DLK seemed to occur more frequently after LASIK performed with the IntraLase 15 kHz femtosecond laser than after LASIK performed with the Moria M2 microkeratome.