We describe the technique of femtosecond-assisted astigmatic keratotomy (AK) in a post-keratoplasty patient with irregular, nonorthogonal astigmatism. Using the keratoplasty software, an anterior arcuate side cut (400 mum thick, 6.5 mm diameter) was created using the femtosecond laser in a 68-year-old woman with irregular astigmatism 28 years after penetrating keratoplasty for keratoconus. No intraoperative or postoperative adverse events were seen during the follow-up period. Six months after the procedure, the uncorrected visual acuity improved from 20/60 to 20/50 and the best spectacle-corrected visual acuity, from 20/50 to 20/32. The mean manifest astigmatic correction decreased from 4.00 diopters (D) to 0.50 D; corneal topography showed a significant improvement in irregular astigmatism. The technique of femtosecond-assisted AK is simple and efficient for managing irregular and nonorthogonal astigmatism in post-keratoplasty patients and may overcome the limitations of earlier techniques.