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To determine the factors associated with sporadic diffuse lamellar keratitis (DLK) after microkeratome laser-assisted in situ keratomileusis (LASIK).This large database retrospective study included consecutive cases of LASIK performed between 2007 and 2016 at Care-Vision Laser Centers, Tel-Aviv, Israel. Patients were divided into 2 groups according to whether or not they subsequently developed DLK.A total of 24,026 eyes of 12,013 patients with a mean age of 32.9 ± 10.3 years were included. Post-LASIK DLK developed in 464 eyes (1.9%), and the annual rate decreased from 7.1% (2007) to 1.7% (2016) (P < 0.001). The DLK group had a higher proportion of males (58.5% vs. 52.1%, P = 0.006), greater preoperative central corneal thickness (549.5 ± 32.6 vs. 545.3 ± 30.5 μm, P = 0.005), and a lower proportion of high astigmatism (>3 D) (0.4% vs. 1.6%, P = 0.05). The DLK group had a higher proportion of previous LASIK treatment (2.8% vs. 1.3%, P = 0.006), Moria M2 (rather than the SBK) microkeratome (71.1% vs. 34.0%, P < 0.001), smaller suction ring number (P < 0.001), greater stop size (P < 0.001), and greater flap thickness (119.2 ± 50.4 vs. 110.8 ± 22.2, P = 0.007). In multivariable analysis, a smaller suction ring number [odds ratio (OR) 0.89, P = 0.04], Moria M2 microkeratome (OR 5.26, P < 0.001), larger optical zone (OR = 2.04, P = 0.01), and higher spherical equivalent (OR = 1.08, P = 0.02) were associated with DLK.In the modern LASIK era, the incidence of DLK continues to decrease. Higher preoperative ametropia, smaller suction ring number, an older type of microkeratome, and larger optical zones are associated with higher DLK rates after LASIK.