Background: The Premier Perspective Database (Premier Inc, Charlotte, NC) was used to compare hospital costs and perioperative outcomes for video-assisted thoracoscopic surgery (VATS) and open lobectomy procedures in the United States. Methods: Eligible patients underwent a lobectomy for cancer by a thoracic surgeon, by VATS or open thoracotomy and were captured in the database between third quarter of 2007 and through 2008. Multivariable logistic regression analyses were performed for binary outcomes. Ordinary least-squares regressions were used to estimate continuous outcomes. All models were adjusted for patient and hospital characteristics. Results: A total of 3,961 patients underwent a lobectomy by a thoracic surgeon by open (n = 2,907) or VATS (n = 1,054) approach. Hospital costs were higher for open versus VATS; $21,016 versus $20,316 (p = 0.027). Adjustment for surgeon experience with VATS over the 6 months prior to each operation showed a significant association between surgeon experience and cost. Average costs ranged from $22,050 for low volume surgeons to $18,133 for high volume surgeons. For open lobectomies, cost differences by surgeon experience were not significant and both levels were estimated at $21,000. Length of stay was 7.83 versus 6.15 days, for open versus VATS (p = 0.000). Surgery duration was shorter for open procedures at 3.75 versus 4.09 for VATS (p = 0.000). The risk of adverse events was significantly lower in the VATS group, odds ratio of 1.22 (p = 0.019). Conclusions: Lobectomy performed by the VATS approach as compared with an open technique results in shorter length of stay, fewer adverse events, and less cost to the hospital. Economic impact is magnified as the surgeon's experience increases.