To report on a patient with uncorrectable fluctuating astigmatism from multiple previous radial keratotomy (RK) procedures who successfully underwent a femtosecond laser-assisted deep anterior lamellar keratoplasty (DALK) with big-bubble technique. A 60-year-old woman with a history of multiple RK procedures with 16 radial incisions and 4 Ruiz-style cuts had fluctuating corneal astigmatism with preoperative best contact lens-corrected visual acuity of 20/80. Intraoperatively, a femtosecond laser-assisted zigzag pattern DALK was performed. Descemet baring was successfully achieved using the big-bubble technique without air escaping from the radial incisions, likely related to precise depth of base of posterior side cut made by laser. Postoperative best-corrected visual acuity is 20/25 with 1.3 diopter of astigmatism at 5 months. To our knowledge, this is the first report to use this technique in a cornea with RK incisions. Femtosecond lasers may promote the success of DALK in challenging corneas.