The purpose of this study was to compare weight gain and food intake during high-fat feeding in outbred CD-1 male mice while considering several different experimental designs. This study was completed using data from three separate experiments and was designed to address different experimental design issues. Experiment 1 compared mice housed in groups or singly. Experiment 2 compared adolescent and young adult mice. Experiment 3 examined mice that had been previously exercise-trained prior to diet-induced weight gain. Data from each experiment were analysed using repeated measures analysis of variance and linear regression. While housing and age did not significantly affect weight gain, mice that were previously exercise-trained consumed significantly more kilocalories than sedentary mice while maintaining comparable body weights. We generated a linear prediction model using data from Experiments 1 and 2 that will allow investigators to calculate the weeks of high-fat feeding needed to reach a target body weight. Our key findings characterize the issues related to and affecting experimental design when utilizing an outbred mouse diet-induced weight gain model and will serve as a guide for future researchers.