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Purpose: To compare postoperative evolution of visual acuity, flap thickness, and stromal optical density during the first 3 months after femtosecond (FS) laser in situ keratomileusis surgery for correction of myopia using the iFS 150-kHz FS laser and LenSx FS laser platforms. Methods: This was a prospective case series. Thirty-nine eyes treated with the iFS 150-kHz FS laser versus 38 refraction-matched eyes treated with the LenSx FS laser platform were included. Visual outcomes, flap morphology, and optical density of the stroma (in both flap and residual stromal bed) were compared at 4 visits during a three-month follow-up period. Results: No significant differences were found in uncorrected distance visual acuity in any of the follow-up visits (1 day −0.02 vs. −0.03; 1 week −0.04 vs. −0.03; 1 month −0.04 vs. −0.04; 3 months −0.03 vs. −0.05 logarithm of the minimum angle of resolution). Flaps created with the iFS 150-kHz FS laser were closer to the intended thickness (110 μm) in every postoperative comparison (1 day 108.6 vs. 124.3; 1 week 107.6 vs. 123.6; 1 month 110.4 vs. 126.8; 3 months 116.2 vs. 126.5 μm; P < 0.0001). Dispersion of values, standard deviation, intraflap range, and differences in symmetric points were lower in the iFS 150-kHz FS laser group. Flap stromal optical density was significantly higher in the LenSx FS laser group at day 1 and week 1 (134.5 vs. 158.9 gray scale unit [GSU]; P < 0.0001 and 144.8 vs. 160.1 GSU; P = 0.011, respectively). Residual stromal bed optical density was higher in the LenSx FS laser group at all postoperative visits, and the differences reached significance at 1 week postoperatively (121.9 vs. 135.4 GSU; P = 0.03). Conclusions: Although both devices provided satisfactory visual outcomes, significant differences were detected in flap parameters. Flaps made with the iFS 150-kHz FS laser were thinner, more uniform, transparent, and accurate compared with those obtained with the LenSx FS laser.