Lung cancer is the leading cause of cancer death worldwide. Gender differences in lung cancer outcomes are known. When compared to men, women have significantly better survival and women are more likely to develop lung cancer when nonsmokers. Research suggests estrogen plays a key role in the risk of development and outcomes of lung cancer. Accordingly, anti-estrogen use should also influence survival in female non-small cell lung cancer (NSCLC) patients. In this study we compared mortality among anti-estrogen users and non-users. METHODS: This population-based study had a retrospective study design. Using the Manitoba Cancer Registry (MCR) we identified all women diagnosed with NSCLC from 2000-2007. The Drug Program Information Network (DPIN) was accessed to establish patients that received anti-estrogens. Demographic data (e.g. smoking patterns, stage, histology) was gathered by chart review. Mortality rates for anti-estrogen users and non-users were compared using Kaplan-Meier survival functions and Cox regression models. RESULTS: 2320 women fit our patient criteria, of which 156 had received prior anti-estrogens. A positive smoking history was documented in 88%, 62% being former vs. 26% current smokers. A history of 30+ packyears was seen in 55%. Exposure to anti-estrogen was associated with a significantly decreased mortality (HR 0.718, p = 0.0031). Overall survival with anti-estrogen vs. none resulted in median survival of 1.89 vs. 0.93 years, respectively (p < 0.0001). CONCLUSIONS: Our results demonstrate that anti-estrogens are associated with decreased mortality from NSCLC. These findings supplement and reinforce past evidence that estrogen plays a key factor in the biology and outcomes of NSCLC.