Nonmedical use of prescription-stimulant medication such as methylphenidate (MPH) has increased among college students over the past several years. Common motivations for use include enhancements in cognition and subjective arousal. As it is unclear whether stimulant medication exerts the same effect on healthy individuals as for those with attention-deficit/hyperactivity disorder, it is possible that many reported effects of prescription stimulants by healthy individuals may stem from placebo effects, which may be an important mechanism underlying initiation and maintenance of nonmedical use. This study examined whether placebo effects influence reports of subjective mood and cognitive performance among college students who endorsed several risk factors for prescription-stimulant misuse (i.e., low grade point average, fraternity/sorority involvement, binge drinking, cannabis use). Ninety-six subjects (60% male) completed cognitive tests and questionnaires assessing present mood state on two occasions. Forty-seven participants were randomized to an experimental condition and orally ingested what they believed to be MPH, though actually placebo, on one visit and received no medication on the other visit. The control group received no medication on either visit. During the administration visit, experimental participants reported feeling significantly more high and stimulated compared with the nonadministration visit and to the control subjects. However, cognitive enhancement differences were not generally seen between visits or groups. This research demonstrates that placebo effects for prescription stimulants do influence subjective mood and may be implicated in nonmedical stimulant use. This knowledge may be useful in challenging prescription-stimulant-related expectancies to decrease the prevalence of use among college students.