Purpose. To assess the intraoperative results comparing two non-mechanical laser assisted penetrating keratoplasty approaches in keratoconus and Fuchs dystrophy. Patients and Methods. 68 patients (age 18 to 87 years) with keratoconus or Fuchs dystrophy were randomly distributed to 4 groups. 35 eyes with keratoconus and 33 eyes with Fuchs dystrophy were treated with either excimer laser ([Exc] groups I and II) or femtosecond laser-assisted ([FLAK] groups III and IV) penetrating keratoplasty. Main intraoperative outcome measures included intraoperative decentration, need for additional interrupted sutures, alignment of orientation markers, and intraocular positive pressure (vis a tergo). Results. Intraoperative recipient decentration occurred in 4 eyes of groups III/IV but in none of groups I/II. Additional interrupted sutures were not necessary in groups I/II but in 5 eyes of groups III/IV. Orientation markers were all aligned in groups I/II but were partly misaligned in 8 eyes of groups III/IV. Intraocular positive pressure grade was recognized in 12 eyes of groups I/II and in 19 eyes of groups III/IV. In particular, in group III, severe vis a tergo occurred in 8 eyes. Conclusions. Intraoperative decentration, misalignment of the donor in the recipient bed, and need for additional interrupted sutures as well as high percentage of severe intraocular positive pressure were predominantly present in the femtosecond laser in keratoconus eyes.