Purpose: To determine the refractive predictability, stability, efficacy, and complication rate of femtosecond laser-enabled astigmatic keratotomy for post-keratoplasty astigmatism. Design: A retrospective case series (pilot study). Participants: Thirty-seven eyes of 34 patients. Methods: All eyes underwent IntraLase-enabled astigmatic keratotomy for high astigmatism (>5 diopters [D]) after penetrating keratoplasty. Main Outcome Measures: Uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), manifest refraction, higher-order aberrations, and complications. Results: Mean follow-up was for 7.2 months. Uncorrected visual acuity improved from a mean of 1.08±0.34 logarithm of the minimum angle of resolution preoperatively to a mean of 0.80±0.42 postoperatively (P=0.0016). Best-corrected visual acuity improved from a mean of 0.45±0.27 preoperatively to 0.37±0.27 postoperatively (P=0.018). The defocus equivalent was significantly reduced by more than 1 D (P=0.025). The value of absolute astigmatism was reduced from 7.46±2.70 D preoperatively to 4.77±3.29 D postoperatively (P=0.0001). Higher-order aberrations were significantly increased. The efficacy index was 0.6±0.6. There were no cases of perforation, wound dehiscence, or infectious keratitis. Three eyes (8%) experienced an episode of graft rejection. Overcorrection occurred in 9 eyes (24%). Conclusions: IntraLase-enabled astigmatic keratotomy is an effective treatment for high astigmatism after penetrating keratoplasty with an encouraging refractive predictability. Future studies may help refine the treatment parameters required to achieve reduction of cylinder with greater accuracy. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.