Objective: To evaluate the predictability and safety of hypertonic saline (50% sodium chloride)-assisted laser-assisted subepithelial keratectomy (HS-LASEK) vs 20% alcohol-assisted LASER (A-LASEK). Setting: American Laser Medical Center, Rishon Le-Zion, Israel. Methods: Fifty-two consecutive eyes (26 patients) were randomized to HS-LASEK (30 eyes) and A-LASEK (22 eyes) groups. The patients' eyes were examined, refracted, and photographed at 1 day, 5 days, 2 weeks, and 1 month postoperatively by a masked physician. Corneal topography and confocal examination were performed before and 1 month after surgery. Main Outcome Measures: The predictability, accuracy, and visual recovery of HS-LASEK vs A-LASEK in the first postoperative month. Results: The accuracy of HS-LASEK was similar and sometimes better than A-LASEK. Two weeks after surgery, 17 eyes (57%) in the HS-LASEK group and 10 eyes (46%) in the A-LASEK group were within ± 0.5 diopter of the intended refractive correction (P<.05). At all time points eyes in the HS-LASEK group had better best-corrected visual acuity than eyes in the A-LASEK group, although the uncorrected visual acuity was similar. Eighteen (61%) of the HS-LASEK-treated eyes and 12 (55%) of the A-LASEK-treated eyes had an epithelial defect after surgery. The HS-LASEK-treated eyes had significantly larger epithelial defects. The resolution of the defects was faster in the HS-LASEK-treated eyes (mean ± SD, 4.5 ± 0.4 days vs 5.8 ± 0.2 days, P = .002). The subepithelial scar was thicker in A-LASEK-treated eyes. Conclusions: Hypertonic saline-assisted LASEK provides good postoperative accuracy, safety, and a similar rate of complications. In view of recent evidence regarding the epithelial toxic effects of alcohol, HS-LASEK might be a better treatment alternative.