Nontraditional scheduling in the National Football League (NFL) has created variation in the rest/preparation time among opponents. Using data from the 2011 to 2015 NFL seasons, regression analysis examines the impact of differential rest and preparation periods among teams on the probability of the home team winning and on the number of points scored in a particular contest. Results show that the probability of winning a game for the home team and the total number of points scored in a game are impacted by different rest combinations between opponents. These impacts are sensitive to the familiarity among opponents and the travel patterns of the visiting team.