Quality of life is an important treatment outcome for conditions that are rarely fatal, such as cutaneous basal cell carcinoma and squamous cell carcinoma (typically called nonmelanoma skin cancer (NMSC)). The purpose of this study was to compare quality-of-life outcomes of treatments for NMSC. We performed a prospective cohort study of 633 consecutive patients with NMSC diagnosed in 1999 and 2000 and followed for 2 years after treatment at a university-based private practice or a Veterans Affairs clinic. The main outcome was tumor-related quality of life 1 to 2 years after therapy, measured with the 16-item version of Skindex, a validated measure. Skindex scores vary from 0 (best) to 100 (worst) in three domains: Symptoms, Emotions, and Function. Treatments were electrodessication and curettage (ED&C) in 21%, surgical excision in 40%, and Mohs surgery in 39%. Five hundred and eight patients (80%) responded after treatment. Patients treated with excision or Mohs surgery improved in all quality-of-life domains, but quality of life did not improve after ED&C. There was no difference in the amount of improvement after excision or Mohs surgery. For example, mean Skindex Symptom scores improved 9.7 (95% CI: 6.9, 12.5) after excision, 10.2 (7.4, 12.9) after Mohs surgery, and 3.4 (-0.9, 7.6) after ED&C. We conclude that, for NMSC, quality-of-life outcomes were similar after excision and Mohs surgery, and both therapies had better outcomes than ED&C. © 2007 The Society for Investigative Dermatology.