To evaluate the long-term outcome of ocular surface reconstruction, including keratolimbal allograft (KLAL) and amniotic membrane transplantation (AMT) with or without penetrating keratoplasty (PKP), in patients with nonambulatory vision secondary to total limbal stem cell deficiency (LSCD). Retrospective, non-comparative interventional case series. Thirty-nine eyes in 31 consecutive patients with total LSCD, as defined by impression cytology, who had a preoperative best-corrected visual acuity of less than 20/200 and a minimum follow-up of 12 months. Patients were divided into three groups: group 1 (16 eyes) with chemical burns, group 2 (9 eyes) with Stevens-Johnson syndrome (SJS), and group 3 (14 eyes) with other causes of LSCD, including ocular cicatricial pemphigoid, atopic keratoconjunctivitis, and aniridia. All patients underwent KLAL and AMT by one surgeon (SCGT). If needed, PKP was performed at the same surgical setting using tissue from the same donor. Cumulative rates of survival of ambulatory vision (> or = 20/200), survival of KLAL, survival of PKP, and incidence of complications. Fifty-three KLAL with AMT procedures were performed in 39 eyes, of which 23 eyes received simultaneous PKP at the time of the first KLAL. The mean follow-up was 34.0 +/- 21.5 months (range, 12-117.6). The mean period of ambulatory vision was 23.9 +/- 20.9 months (range, 0-104). The overall survival of ambulatory vision was 53.6% at 3 years and 44.6% at 5 years. The survival of ambulatory vision was significantly worse in SJS compared with other causes (67%, 81%, and 92% for groups 1, 2, and 3, respectively; P = 0.06 for group 1 versus 2, P = 0.0008 for group 1 versus 3). KLAL performed alone resulted in higher survival of ambulatory vision at 2 years (86.1% +/- 9.1%) compared with KLAL with PKP (46.9% +/- 10.6%, P = 0.100). The survival of PKP was significantly worse in SJS compared with the other causes (20.0% +/- 17.9% compared with 55.6% +/- 11.7%, respectively, P = 0.028). After 2 years, the survival of the second KLAL was better than that of the first: 68.2% +/- 15.4% compared with 27.3% +/- 13.4%, respectively (P = 0.041). Ambulatory vision for a period of more than 2 years can be achieved by KLAL with or without PKP in eyes with severe ocular surface disorders caused by total LSCD. However, a progressive decline of the visual outcome and graft survival is evident with time. Performing PKP simultaneously with KLAL may be associated with a less favorable outcome. The failure of KLAL is associated with the loss of donor cells in the recipient. Augmentation of ocular surface defense is essential in securing the success of KLAL and PKP. Future modifications of the surgical procedure and of the immune suppressive protocols may improve survival of the allogeneic grafts and the final visual outcome.