Purpose: Prior studies of GIST identified 1,458 cases from 1992-2000, prior to FDA approval of imatinib. Our objective is to conduct a thorough analysis of factors influencing survival and incidence of 5,411 patients with GIST from 1993-2009. Methods: Retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) database from 1993 to 2009. Results: A total of 5,411 cases of GIST were identified, with higher prevalence in men (53.15%) than women (46.85%). Most were white patients (70.21% white, 17.34% black, and 12.46% other). Most had localized disease (51.45%) compared to regional (23.16%) and distant (15.58%). Highest prevalence was in the stomach (54.09%) and small intestine (28.77%). Incidence rate analysis revealed significant increases in yearly rates for the overall population, males, females, whites, blacks, “others,” and stage of disease, however, this may represent increases in diagnosis. Overall average incidence was 0.44 per 100,000 population. Males (0.50) had a higher average incidence rate than females (0.39). Blacks (0.83) had the highest average incidence, followed by “others” (0.68), then whites (0.37). Average incidence of localized disease (0.23) was highest, followed by distant (0.10), then regional (0.07). Average incidence was higher in stomach (0.24) compared to small intestine (0.13). The overall five-year survival between 1993-2009 has shown a steady increase from 53.08% to 75.52%. Overall five-year survival between 1993-1997 was 54.77%, 1998-2003 was 68.41%, 2003-2009 was 75.80%; cox HR analysis showed statistical significance for higher survival in 2003-2009 compared to 1998-2002 (HR 1.38, p<.0001) and 1993-1997 (HR 2.18, p<.0001). Survival was significantly higher in women than men (HR 1.27, p<.0001). Survival was higher in white and “other” compared to blacks, but was not significant. Survival was highest in localized disease, followed by regional (HR 2.18, p<.0001), then distant (HR 5.38, p<.0001). Surgery led to higher survival than without (HR 2.36, p<.0001). Survival of stomach GIST was significantly higher than small intestinal GIST (HR 1.14, p<.05). Conclusion: There were overall increases in incidence and survival from 1993-2009. Survival was significantly higher in woman, localized disease, surgical intervention, stomach GIST, and diagnosis between 2003-2009. Prior studies examined fewer cases and those prior to 2002, before advances in treatment. Our study is the first of its kind to conduct a comprehensive analysis and comparison of factors influencing epidemiology from 1993-2009. Imatinib and sunitinib were FDA approved in 2001 and 2006, respectively. Our reported increase in overall survival from 1993-2009 may reflect effectiveness and recent increase in use of these drugs.