PURPOSE To identify baseline demographic and clinical factors associated with undergoing penetrating keratoplasty (PK) in a prospective cohort of 1,065 keratoconus patients followed for eight years in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study. DESIGN Multicenter, prospective, observational cohort study. METHODS We report the rate of PK over eight years and baseline factors predictive of PK in 1,065 patients who, at the time of study enrollment, had not undergone PK in either eye. RESULTS Eighty-two percent of patients completed the eight-year close-out visit. Twelve percent (126 of 1,065) had PK in one (9.3%) or both eyes (2.5%). Baseline factors associated with increased likelihood of PK included younger age, steeper keratometric values, worse visual acuity, corneal scarring, poorer contact lens comfort, and poorer vision-related quality of life. The percent of eyes undergoing PK was 15% for patients 40 years old and younger, 28% for eyes with a steep keratometric value greater than 52 diopters, 33% for visual acuity less than 20/40, and 24% for eyes with corneal scarring. CONCLUSIONS The CLEK Study confirmed previous reports of the increased likelihood of PK associated with corneal scarring, steeper keratometry values, poorer visual acuity, and poorer contact lens comfort. The CLEK Study is among the first to report an increased risk of PK associated with younger age, worse vision-related quality of life, and flatter contact lens fits. Knowledge of these factors is beneficial to clinicians in patient education and may be useful in disease management.