Purpose To describe the outcomes of limbal stem cell transplantation in eyes with limbal stem cell deficiency related to soft contact lens wear. Design Retrospective interventional case series. Methods Institutional database search at the Cincinnati Eye Institute revealed 9 patients (14 eyes) who underwent limbal stem cell transplantation with systemic immunosuppression for soft contact lens wear–related limbal stem cell deficiency. Outcome measures included patient demographics, symptoms, best-corrected visual acuity, ocular surface stability, adverse events, and additional surgeries required. Results Average patient age at time of surgery was 46.6 ± 11.1 years (range 20–60 years). Average duration of follow-up was 28 ± 19.1 months (range 12–70 months). Preoperative best-corrected visual acuity (BCVA) was 20/40 or worse in all eyes (average 20/70, range 20/40–20/250) and patient symptoms included foreign body sensation, tearing, redness, and/or pain. Four eyes (29%) underwent living-related conjunctival limbal allograft and 10 eyes (71%) underwent cadaver-donor keratolimbal allograft surgery. Topical and systemic immunosuppression was used in all patients. At final follow-up after limbal stem cell transplantation, there was a stable ocular surface in 12 of 14 eyes (86%) and improvement in BCVA to 20/30 or better and complete resolution of patient symptoms in all except 1 patient who had significant rosacea blepharokeratoconjunctivitis, whose BCVA remained at 20/150 and 20/60, in right and left eyes, respectively. The most common adverse event was an increase in intraocular pressure in 8 of 14 eyes (57%), requiring topical antiglaucoma treatment. Ten of 14 eyes (71%) underwent cataract extraction related to topical steroid use. No eyes required subsequent penetrating keratoplasty. Conclusion Limbal stem cell transplantation is a viable option for the management of soft contact lens wear–related limbal stem cell deficiency in young healthy patients. Early intervention prior to subepithelial fibrosis can lead to good visual outcomes with no need for subsequent cornea transplant. Co-management with a solid organ transplant specialist is helpful for the monitoring and management of systemic adverse events related to patient systemic immunosuppression.