Objective: To describe the outcome of penetrating keratoplasty (PK) for corneal opacification in the setting of systemic mucopolysaccharidoses (MPS). Methods: A consecutive case series and literature review. Results: Eight eyes from 5 patients with MPS (MPS I, MPS IV, and MPS VI) and a history of PK met inclusion criteria for our case series at the University of Minnesota Medical Center. The mean age at the time of PK was 40.5 years (range, 11.7-65.3 years). Mean follow-up time after the PK was 4.9 years (range, 1-11 years). Mean (SD) visual acuity before PK was 0.90(0.38) logMAR. The mean (SD) visual acuity at the last visit for all 8 eyes was 0.32 (0.16) logMAR. Visual acuity improved in 7 of 8 eyes (P=.002). Although early rejection led to repeat PK in 1 eye, no recurrent opacity consistent with MPS was noted in any of the corneal grafts. In a literature review, we found 23 reports documenting 40 initial and 3 repeat cases of PK in the setting of MPS. Of these, 31 initial and 2 repeat corneal grafts were reportedly clear during follow-up, ranging from 0.25 to 13 years. Conclusions: Penetrating keratoplasty is often a beneficial intervention in appropriate patients with corneal clouding due to MPS. Improvement in vision can be obtained with stable, clear corneal grafts in this population.