Although sensation seeking or novelty seeking is a reliable predictor of drug use in humans, individual differences in free-choice novelty seeking in animal models have generally failed to predict drug use. In the current article, hierarchical multiple regression analyses were used on data collected from a large sample of rats. Rats were screened on measures of inescapable and free-choice novelty tests and then were trained to lever press for sucrose or intravenous amphetamine. Although scores from the inescapable novelty test weakly predicted responding for amphetamine, the addition of free-choice novelty preference scores into the regression analyses significantly improved the predictive models. These results indicate that, similar to evidence in humans, individual differences in novelty seeking may be able to predict drug use in rats.