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Purpose To compare anterior lamellar keratoplasty (ALK) with the reference surgical technique (penetrating keratoplasty [PK]) for risk of rejection. Design Retrospective, comparative case series. Methods setting: Institutional. patients: One hundred forty-nine consecutive ALK procedures (ALK group) and 149 matched PK procedures (PK group) performed for optical indication in eyes with corneal diseases not involving the corneal endothelium (ie, keratoconus, scars after infectious keratitis, stromal dystrophies, and trauma). main outcome measures: Three-year graft survival and cumulative incidence of rejection episodes. Results The 3-year overall graft survival was 98.3% in the ALK group and 94.3% in the PK group ( P = .03). The 3-year cumulative incidence of irreversible rejection was 0.0% in the ALK group and 5.2% in the PK group ( P = .02). The 3-year cumulative incidence of rejection episodes was 10.0% in the ALK group and 23.2% in the PK group ( P = .01). The average graft-to-rejection episode time was 21.6 ± 22.0 months in the PK group and 19.4 ± 12.7 months in the ALK group ( P = .76). Conclusions ALK techniques dramatically decrease the risk of irreversible endothelial and stromal rejection after corneal transplantation. Immune-mediated rejection episodes are observed after ALK, but its lower graft failure rate compared with PK is at least partly the result of the absence of endothelial rejection. In addition, the incidence of rejection episodes after ALK was 50% less than that observed after PK.