Purpose To evaluate the refractive and keratometric effect of arcuate keratotomy using femtosecond technology in patients with high post-keratoplasty astigmatism with a mushroom profile. Setting Enaim Refractive Center, Tel-Aviv, Israel. Design Noncomparative prospective interventional case series. Methods The arcuate depth incision was set to 80% of the minimal graft thickness, with a 60-degree angle. The mean diameter was 5.79 mm ± 0.32 (SD) according to the graft size. Patient evaluation included logMAR corrected distance visual acuity (CDVA), refraction, keratometry (K), and a complete eye examination. Results Twenty-seven eyes of 27 patients after keratoplasty surgery were included. Both uncorrected distance visual acuity and logMAR CDVA improved after surgery. The preoperative mean logMAR CDVA was 0.29 ± 0.37 (SD), which improved by 1 line (to 0.19 ± 0.10; P =.01). The mean refractive astigmatism was -8.43 ± 2.80 diopters (D) (range -4.5 to -15 D), and it declined at the 3-month postsurgical follow-up to -4.31 ± 0.23 D (P <.001) and remained stable until the end of follow-up (-3.31 ± 1.39 D; P = 1.00). The K value decreased by 1.18 D (P <.001). There were no complications or adverse effects during the follow-up period. Conclusions Arcuate keratotomies performed with the femtosecond laser showed good results. There was a more than 50% decrease in post-mushroom profile keratoplasty astigmatism as well as stability of the results over 1 year. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.