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Introduction: There are limited treatment options for patients with prior pneumonectomy and a new lung malignancy. The safety and efficacy of stereotactic body radiotherapy in this subpopulation has not been well defined. Methods: Postpneumonectomy patients treated with lung SBRT were identified from a prospective single institution database. Treatment toxicity was recorded prospectively using the Common Terminology Criteria for Adverse Events version 3.0. Disease recurrences were categorized as local, regional, or distant metastatic disease. Overall survival was calculated using the Kaplan-Meier method. Results: Of 406 patients, 13 postpneumonectomy patients were identified and 14 tumors were treated with SBRT. Median age was 69 years. Three lesions were biopsy confirmed. The SBRT doses were 60 Gy/3 ( n = 1), 54 Gy/3 ( n = 1), 48 Gy/4 ( n = 7), 60 Gy/8 ( n = 2), and 50 Gy/10 ( n = 3). Median follow-up was 24 months. Two patients had grade 3 radiation pneumonitis 3 and 4 months post-SBRT; they died 3 and 1 months later, respectively, one of myocardial infarction and the other of progressive dyspnea thought to be related to congestive heart failure. There were no local failures, one regional failure, and three distant failures. Median survival was 29 months, 1 and 2 year overall survival were 69% (95% confidence interval: 48–100%) and 61% (95% confidence interval: 39–95%), respectively. Conclusions: SBRT in patients with prior pneumonectomy poses challenges because of limited lung reserve. However, local control and long-term survival can be achieved using SBRT in this inoperable population. Careful consideration must be given to radiation planning to minimize the risk of radiation pneumonitis.