OBJECTIVES: To characterize real-world medical resource utilization and costs following initiation of anti-cancer treatments for patients with Stage IB-IV Non-Small Cell Lung Cancer (NSCLC). METHODS: A retrospective, longitudinal, open-cohort study design was chosen using Medicare linked Surveillance Epidemiology and End Results (SEER) data. All Medicare-eligible patients in the SEER registry who were diagnosed with NSCLC during 2005–2007 and treated with anti-cancer therapy were identified. The observation period spanned from NSCLC diagnosis through the earliest date of end of anti-cancer therapy, data end date, or death. All-cause and NSCLC-related utilization and costs were reported, stratified by hospitalization, emergency room (ER), and outpatient visits. Results were stratified by patients with non-advanced cancer (Stages IB-IIIA) and advanced cancer (Stages IIIB-IV). Pharmacy costs were reported for patients diagnosed with NSCLC in 2007. RESULTS:  The study population consisted of 6,365 patients; mean (SD) age was 73.7 (5.4) years, 54% were males, and median follow-up was 351 days. The all-cause rate per patient per month (PPPM) was 0.14, 0.10, and 4.08; NSCLC-related PPPM rate was 0.12, 0.05, and 2.86 for hospitalization, ER, and outpatient, respectively. The median monthly length of stay (days) for hospitalization was 1.25 for all-cause and 1.0 for NSCLC-related stays. The mean all-cause PPPM costs were $4,989 (hospitalization: $2,278, ER: $54, outpatient: $2,657). The mean NSCLC-related PPPM costs were $4,032 (hospitalization: $1,721, ER: $23, outpatient: $2,288). The mean all-cause PPPM costs were $3,805 ($2,873 NSCLC-related) for patients with non-advanced cancer and $5,822 ($4,847 NSCLC-related) for patients with advanced cancer. All-cause PPPM prescription drug costs were $560. CONCLUSIONS: The SEER-Medicare database analysis found that in Stage IB-IV NSCLC patients, NSCLC-related costs accounted for over 80% of all health care costs while patients were on anti-cancer therapies. Higher costs were incurred by patients diagnosed with advanced NSCLC as compared to patients diagnosed with non-advanced disease.