Several recent studies have reported a considerably higher overall survival (OS) rate in females in various geographic regions This study further investigates the characteristics of melanoma that contribute to OS of women residing in the United States. Chi-square, Kaplan-Meier, and Cox regression models were used to analyze differences in demographics, treatment, and survival of invasive cutaneous melanoma in men and women diagnosed from 2004 to 2016 in the National cancer database. In 316 966 patients met inclusion criteria. Men had a significantly higher median age of diagnosis at 61 years (interquartile range or IQR: 51-72) in comparison to women where the median age of diagnosis was 55 years (IQR: 43-68) (P <.0001). The most common primary site for men was the trunk (35.5%), whereas the lower extremities were the most common primary site for women (30.3%). Women had a higher 5 year (82.6%) and 10 year (73.1%) OS compared to 5 year and 10 year OS of 72.2% and 58.7%, respectively, in men (P <.0001). When adjusting for confounders, female gender was independently associated with improved OS (ref: male HR = 0.791; 95% confidence interval 0.773-0.809; P <.0001). Overall, we conclude that female gender is an independent favorable prognostic factor for melanoma survival.