Traditional dogma is that men have a higher metabolism compared to women. Because of an increased obesity rate in women, the purpose of this study was to test the hypothesis that compared to males, females will gain more body weight per gram of food consumed. Methods: To test our hypothesis male and female mice were fed either a high or low-fat diet for 20-weeks, while monitoring food intake and body weight. At the end of the 20 week feeding plan, a final weight on the mice was taken, as well as a measurement from the nose to rump of the mouse in order to calculate a BMI. Results: Male mice consistently consumed more food than female mice, regardless of the diet. As expected mice on the high-fat diet gained more weight than mice on the low-fat diet. Further, on the low-fat diet male mice gained more weight than the female mice. Interestingly, there was no difference between the amount of weight gain between male and female mice on the high fat. However, within the same diet, male mice gained more weight per gram of food consumed. On average, male mice gained approximately double the body weight per gram of food consumed compared with female mice (51 vs. 27 mg of body weight per gram of food consumed). Conclusions: We had hypothesized that increased food intake in male mice would primarily account for the differences in body weight between male and female mice. However, contrary to our hypothesis, the data shows that male mice gained more body weight per gram of food consumed. This finding provides a novel hypothesis to explain the mechanism by which, at least in rodents, females are more resistant to obesity. Future studies comparing metabolic rate and physical activity levels will need to be performed to explore this finding further.