Stereotactic body radiotherapy (SBRT) provides excellent local control of lung lesions, though local failures (LF) occur in 10-30% of patients. A retrospective review was conducted to determine the safety and efficacy of a second course of SBRT for locally recurrent lung lesions. The records of all patients completing two courses of SBRT at the University of Rochester from December 2000 to February 2010 were reviewed. Patients who underwent retreatment with SBRT for a LF in the lung (within 1 cm of the original gross tumor volume) were included in this study. Treatments were performed with the Novalis linear accelerator, using the ExacTrac system for localization. All doses were prescribed to isocenter. A planning treatment volume, with a 7 mm axial and 10-11 mm craniocaudal expansion, received 80% or greater of the prescription dose. A total of 25 tumors in 23 patients were treated with two courses of SBRT. Median age was 69 yrs. The retreated tumors were from medically inoperable stage I lung cancer (n = 8), stage II-IV lung cancer (n = 9), or oligometastatic disease from a non-lung primary (n = 8). Six lesions were central, 19 were peripheral. Median lesion size before the first treatment was 2.4 cm (mean 2.8). Median (mean, range) prescribed dose for the first course of SBRT was 50 Gy (50.8 Gy, 35-60 Gy) in 10 (10.2, 5-13) fractions. Initial partial or complete response, before subsequent recurrence, was seen in 13 tumors (52%). Median time to LF after the first treatment was 15 months. Recurrence was determined by RECIST criteria (n = 7), increased FDG avidity on PET (n = 6), or both (n = 12). The median (mean, range) prescribed dose for the second course of SBRT was 50 Gy (47.2 Gy, 30-60 Gy) in 10 (9.8, 5-12) fractions. Median (mean) time to last follow-up or death after the second course of SBRT was 7.4 months (10.4 months). Crude overall survival was 43%. Crude local control was 80% (88% for early stage lung cancer, 78% for advanced lung cancer, and 78% for other oligometastatic disease). At retreatment, size >3 cm and central tumor location trended toward association with worse local control (p<0.10). After retreatment, chest wall pain was seen in 3 patients (all grade II), and symptomatic radiation pneumonitis was seen in 5 patients (3 grade II, 1 grade III, 1 grade V). Probable grade V pneumonitis was seen in 1 patient with a previous diagnosis of lymphocytic interstitial pneumonitis, 11 months after retreatment to 40 Gy in 5 fractions. At retreatment, size >3 cm and a diagnosis of COPD were associated with development of grade II or higher toxicities (p<0.05). A second course of SBRT after LF is a viable option to improve ultimate local control. Toxicity after retreatment is more acceptable with smaller lesions using greater than five fractions.