Background: The effect of gender in sarcoma patients in various organ systems has been the subject of several studies, many of which show no overall survival (OS) difference between male and female genders. Tumor size and grade have been noted to be independent predictors of local recurrence and disease specific survival in a prospective study of patients with non-uterine leiomyosarcoma by Gaddy et. al. however, gender had no effect on OS. Methods: The 2004-2016 National Cancer Database (NCDB) was queried for males with leiomyosarcoma (LMS) and females with extrauterine leiomyosarcoma (EULMS) using topographical codes C490-C496, and C498-C499. Data included: patient’s age, race, year at diagnosis, tumor grade, size and stage, lymph node involvement, receipt of surgical treatment, chemotherapy or palliative care treatment, surgical margins, time to treatment in days, OS (months between the date of diagnosis and date of death or censored at last contact), and long-term survival defined as survival for 60 months or more. Univariate analysis was used to determine significant predictors of binary survival status (i.e. alive or dead), significant factors were then included in a multivariate analysis. Using Stata/SE 15.1, Kaplan-Meier (KM) method with log-rank test was used to compare and estimate OS rates between the 2 groups. Results: The total number of patients was 13537, with 6311 males (46.6%) and 7226 females (53.4%). The OS in females was 57.2 months compared to 72.0 months in males (P < 0.001). Men were also more likely to achieve long-term survival (36.1%) compared to females (34.4%, P < 0.001). Men with LMS had a lower percentage of chemotherapy use compared to females (18.7% vs 25% respectively, P < 0.001) and palliative care use (3.0% vs 3.5%; P = 0.013). Lower likelihood of survival among both groups was noted in older age (OR = 0.96; P < 0.001 in males; OR = 0.97, P < 0.001 in females), tumor stage > I (OR = 0.64, P = 0.005 in males; OR = 0.56, P < 0.001 in females) and positive surgical margins (OR = 0.76, P = 0.013 in males; OR = 0.87, P = 0.009 in females). Contrarily, increasing year of diagnosis was associated with an increased likelihood of survival (OR = 1.51, P < 0.001 in males; OR = 1.27, P < 0.001 in females). Larger tumor size was also associated with decreased likelihood of survival, but only in the female group (OR = 0.39, P = 0.001). Conclusions: Our analysis shows that males with LMS had a higher OS and higher percentage of long-term survival compared to females. The only factor affecting survival that was different between the 2 groups was the tumor size, which was associated with significantly decreased likelihood of survival in females. No clear explanation for this different survival could be extrapolated from the clinical data collected. Further studies are recommended to investigate the genetic, epigenetic, and possibly hormonal factors that may affect survival in LMS.