Positron emission tomography (PET-CT) is valuable for diagnosing early stage non-small cell lung cancer (NSCLC) in the absence of biopsy. Here we investigate the diagnostic, prognostic, and treatment response of PET-CT in NSCLC treated with empiric stereotactic body radiotherapy (SBRT). We retrospectively reviewed 78 empiric lung SBRT cases with pre-treatment PET scans treated to biologic equivalent dose≥100 Gy10. We correlated pre and post-treatment standard uptake values (SUV) with local, regional, and distant control. Statistical analysis was conducted via SPSS v20. A total of 44 males and 34 females median age 77 were treated to 48 Gy in 4 fractions (n=47) or 50 Gy in 5 fractions (n=31). Lung nodules were 1.6 cm (0.6–4.5 cm) with a median planning target volume of 19.1 cc (3.7-97.4 cc). Median pre-treatment SUV=4.1 (0-20). Of the 43 patients with post-treatment PETs, median SUV = 2.7(0-7.2) or 53%(0-302%) of the pretreatment SUV. The median follow-up was 18 months with a 3-year survival of 50% for all patients. Local, regional, and distant control rates at 3 years were 91%, 81%, and 78%, respectively. Relative sisease control for pre-treatment SUV ≤4.0 compared to >4.0 is shown in Table 1: There was no difference in tumor size, location, nodule morphology, or prior cancer/smoking history between patients with pre-treatment SUV ≤ 4 (n=40) and > 4 (n=38). Receiver operating characteristic curve analysis identified optimal SUV cutoff values of 6.0, 3.5, and 4.0 to predict local, regional, and distant failure, respectively. Post-SBRT PET scans with SUV reduction ≥50% demonstrated a 2-year freedom from progression of 89% compared to 57% with SUV reduction <50% (P=0.08). Our study demonstrates a strong correlation between initial PET avidity and regional/distant recurrence, and a trend with local recurrence. Perhaps patients with pretreatment SUV>4 warrant a mediastinal evaluation or closer vigilance in follow-up, though this warrants prospective investigation.