Background: Facial angiofibromas in tuberous sclerosis have been managed with various treatment modalities, including carbon dioxide (CO₂) laser resurfacing. Objective: Our purpose was to perform a long-term clinicopathologic assessment of CO₂ laser treatment of angiofibromas. Methods: This was a retrospective case review of 10 patients treated with a scanning CO₂ laser to flatten lesions. Baseline clinical photographs and those taken at 6, 12, and 24 months after the operation were assessed by a blinded observer. Patients also evaluated outcomes. Biopsy specimens taken immediately and at 4 months after the operation were reviewed. Results: Three groups of patients were identified: the first comprised 2 patients with sustained excellent and good outcomes. A second group (3 patients) had excellent outcomes in the early and medium term but then demonstrated partial deterioration. The last group (5 patients) had a range of early results with invariably poor outcomes at 24 months. In contrast, patients' self-assessment at 24 months was good or excellent in 8 of 10 cases. All biopsy specimens taken immediately after the procedure demonstrated ablation extending into the papillary dermis. Residual angiofibromas were present in 6 biopsy specimens. At 4 months, all biopsy specimens showed a band of superficial dermal fibrosis, but distinguishing between this and adjacent angiofibromas was often difficult. Long-term side effects included 2 cases of subtle hypopigmentation. Conclusion: The long-term results of CO₂ laser treatment of angiofibromas are unpredictable. The marked improvement obtained at 6 months is sustained in only a minority of cases at 24 months. Despite this, patient satisfaction appears relatively high. Initial clinical improvement may be the result of a combination of destruction of angiofibromas and their sequestration under postoperative fibrosis. The benefits of therapy should be weighed against both early morbidity and the risks of long-term complications such as scarring and hypopigmentation. (J Am Acad Dermatol 2001;45:731-5.)