Background: Lobectomy for patients with clinical stage I non-small cell lung cancer (NSCLC) can be performed by thoracotomy or by video-assisted thoracoscopic surgery (VATS). We compared the operative characteristics and postoperative course for patients with clinical stage I NSCLC who underwent lobectomy by VATS or thoracotomy. Methods: We retrospectively reviewed the charts of all patients undergoing lobectomy for clinical stage I NSCLC from January 1, 1998, through June 30, 2005. Results: We performed 147 lobectomies (88 thoracotomy, 59 VATS) in 147 patients with clinical stage I NSCLC. Patient demographics were similar between groups; however, VATS patients had more hypertension (p = 0.0114), chronic renal insufficiency (p = 0.0479), and previous malignancies (p = 0.0086). The two groups did not differ in pathologic stage, tumor size, histologic results, or number of positive nodes. More total nodes were identified in thoracotomy patients (p = 0.0001), and they had a shorter intensive care unit stay (p = 0.0224). VATS patients had significantly less postoperative pneumonia (p = 0.0023). VATS patients trended toward fewer chest tube days and a shorter hospital length of stay. The two groups did not differ in operative time, blood loss, atrial fibrillation, or number of ventilator days. Median survival between the cohorts was similar (>7.9 years thoracotomy versus >4.6 years VATS, log-rank p = 0.6939). Conclusions: Patients undergoing VATS lobectomy for clinical stage I NSCLC, despite having more comorbidities, had fewer postoperative complications. The approaches are equivalent in operative time, blood loss, length of stay, and survival rate. Compared with thoracotomy, VATS lobectomy for patients with clinical stage I NSCLC appears to be a less morbid operation.