Background: Drug policies aimed at youth often adopt “scare tactics” approaches, which highlight harms of substances to dissuade youth from using them. However, the success of deterrent approaches remains widely debated, and some scholars have cautioned that these approaches may do more harm than good. Methods: Drawing on a sample of adolescents from the 2016 Monitoring the Future study, we investigated the influence of perceived drug harmfulness alongside several other risk factors for substance use. Logistic regression models assessed the relative influence of perceived harmfulness, access, peer use, and disapproval on youths’ past year use of marijuana, crack cocaine, and powder cocaine. Results: Perceived drug harmfulness was no longer associated with the use of marijuana and crack cocaine when considering other risk factors. Perceptions of harmfulness were only related to powder cocaine use. In addition, the impact of peer use, access, and disapproving attitudes varied by substance examined. Conclusions: Regarding marijuana and crack cocaine, we find evidence against the deterrence perspective and show that focusing solely on the harms of using a substance may not be an effective policy approach in reducing the use of these substances among adolescents. Programs may also perhaps increase their efficacy by adopting substance-specific approaches.