Background Frailty associated with aging increases the risk of falls, disability, and death. We investigated gender-associated factors for frailty. Methods Data of 3,079 geriatric subjects were retrieved from the National Health and Nutrition Examination Survey (NHANES) 2007–2010 database. After excluding 1,126 subjects with missing data on frailty, medical history and survival, data of 1,953 patients were analyzed. Main endpoints were frailty prevalence, mortality rates and causes of death. Results Frailty prevalence was 5.4% in males, 8.8% in females. Significant risk factors for geriatric frailty in males were being widowed/divorced/separated, low daily total calorie intake, physical inactivity, sleeping >9 h, smoking and hospitalization history; and in females were obesity, physical inactivity, sleeping <6 h, family history of diabetes and heart attack, and hospitalization history. Frail subjects had higher mortality rates (22.5% male; 8.5% female) than pre-frail (8.7% male; 6.4% female) and non-frail (5.4% male; 2.5% female). Main causes of death were heart diseases (41%) and chronic lower respiratory diseases (23.0%) in males and nephritis/nephrosis (32.3%) and chronic lower respiratory diseases (17.6%) in females. Discussion Factors associated with frailty differ by gender, with higher frailty prevalence in females and higher mortality in males. Gender-associated factors for frailty identified in this study may be useful in evaluating frailty and guiding development of public health measures for prevention. Key Message Common predictive factors for frailty among older adults of both genders, including more frequent previous hospitalizations, physical inactivity, and certain gender-associated factors for frailty, are consistent with results of other NHANES studies in which self-reported higher levels of illness and sedentary behavior were directly associated with frailty.