Objective: As the mean age in patients with non-small cell lung cancer increases, the proportion of patients with serious comorbidity who are considered for surgical resection also increases. Patients with non-small cell lung cancer have been shown to have a higher burden of comorbidity than do patients with tumors of other sites, such as breast, prostate, colon, and head and neck. The goal of this review was to determine the impact of comorbidity on postoperative and long-term survival after surgical resection in patients with stage I non-small cell lung cancer. Methods: A database analysis of our hospital's tumor registry included 451 patients who underwent surgical resection for pathologic stage I non-small cell lung cancer between January 1, 1994, and December 31, 1999. Comorbidity severity was prospectively determined with the Kaplan-Feinstein Index. Survival data were collected for each patient from the date of operation, with a mean duration of follow-up of 35.7 months. Bivariate statistics and Cox proportional hazards model analyses were used. Results: The mean age was 64.4 years, and 249 (55%) patients were male. The distribution of overall comorbidity severity was none, 142 (31.5%); mild, 150 (33.3%); moderate, 115 (25.5%); and severe, 44 (9.8%). The overall in-hospital mortality was 2.2% (n = 10/451). There was a nonsignificant trend toward higher hospital mortality with greater comorbidity: none, 0.7% (n = 1/142); mild, 3.3% (n = 5/150); moderate, 0.9% (n = 1/115); and severe, 6.8% (n = 3/44, P = .055). Kaplan-Meier estimated survivals at 3 years for each level of comorbidity were as follows: none, 85.6%; mild, 74.8%; moderate, 68.8%; and severe, 70.0% (P < .002). After adjustment for age, sex, T status, and tumor histologic type, the relative risks of death as a function of comorbidity were mild, 1.44 (95% confidence interval 0.89-2.34); moderate, 2.28 (95% confidence interval 1.43-3.65); and severe; 1.94 (95% confidence interval 1.023-3.70). Conclusions: Comorbidity has a significant impact on survival after surgical resection of patients with stage I non-small cell lung cancer. These data may help to explain the lower than expected survival results for patients after surgical resection for stage I non-small cell lung cancer.