Purpose: To compare two-year results of femtosecond laser assisted LASIK (femto-LASIK) and photorefractive keratectomy (PRK) in terms of astigmatism correction in patients with less than 2. 0 diopters (D) of spherical error and more than 2. 0 D of cylinder error. Methods: In this retrospective study, data were extracted from 100 patient charts. The two study groups were matched by age, gender, and baseline uncorrected distance visual acuity (UDVA) and refractive astigmatism (RA). Preoperative astigmatism was categorized as mild: 2. 00 to <3. 00 D, moderate: 3. 00 to <4. 00 D, and severe: 4. 00 D. Results: Mean RA in the femto-LASIK and PRK groups was respectively 3. 15 ± 0. 94 D ( 7. 00 to 2. 00 D) and 3. 29 ± 0. 95 D ( 6. 25 to 2. 00 D) at baseline (P ¼ 0. 284), and 0. 61 ± 0. 40 D and 0. 62 ± 0. 60 D one year after surgery (P ¼ 0. 674), but significantly lower in the femto-LASIK group ( 0. 61 ± 0. 39 vs. 0. 83 ± 0. 56 D, P ¼ 0. 021) at 2 years when the rate of residual astigmatism more than 1. 0 D was 6. 3% in the femto-LASIK and 19. 6% in the PRK group (P ¼ 0. 046). Mean UDVA in the femto-LASIK group (0. 02 ± 0. 05 logMAR) was better than the PRK group (0. 06 ± 0. 10 logMAR) (P ¼ 0. 025). Mean corrected distance visual acuity (CDVA) was not significantly different between groups (0. 01 ± 0. 03 vs. 0. 01 ± 0. 04 logMAR, P ¼ 0. 714). Both groups had 1e4 Snellen lines CDVA improvement. The three subgroups of baseline astigmatism did not differ significantly in terms of residual astigmatism (all P > 0. 05). However, in subgroups with 4. 00 D cylinder, there was less astigmatic regression at 1 year in the femto-LASIK group (0. 28 ± 0. 43 D) than the PRK group (0. 54 ± 0. 68 D) (P ¼ 0. 007). Conclusions: Our results pointed to better two-year results with femto-LASIK in the treatment of different degrees of astigmatism. UDVA improvement was superior with femto-LASIK, but the two methods did not significantly differ in terms of CDVA improvement.