Despite the general trend of declining use of traditional cigarettes among young adults in the United States, alternative high school students continue to smoke cigarettes and electronic cigarettes at rates much higher than do students attending regular high schools. Challenging life circumstances leading to elevated levels of negative affect may account for increased smoking behavior in this population. Further, a belief in the negative affect-reducing qualities of nicotine may mediate this effect. The current study tested the hypothesis that negative reinforcing outcome expectancies mediate the relationship between negative affect on smoking susceptibility in nonusers, smoking frequency in users, and smoking experimentation in the overall sample. Results support the hypothesis that negative affect in alternative high school students is correlated with smoking experimentation, smoking willingness, and smoking frequency and that the relationship between negative affect and smoking behavior outcomes is mediated by negative reinforcing outcome expectancies (i.e., beliefs in the negative affect-reducing effects of smoking). This finding was supported for both cigarettes and electronic cigarettes and coincides with a rapid increase in the number of high school students nationally who have experimented with electronic cigarettes. Future antismoking initiatives directed at at-risk youth should consider integrating healthier negative affect reduction techniques to counter the use of nicotine products.