Background: Since 2000, heroin use patterns have shifted within the United States. How this change may relate to polydrug use among local heroin users is unknown. Although polydrug use has been studied, user perceptions of drug use in terms of health risks, arrest risk, availability, cost, liking, and dependence have not been considered. Methods: Data are presented from a brief, face-to-face survey conducted in 2016 of 200 non–in-treatment heroin users from Cleveland, OH. We assessed the use of and attitudes on alcohol, marijuana, methamphetamine, heroin, crack cocaine, powder cocaine, and prescription drugs. We estimated polydrug (concurrent past month) use with cluster analysis and latent profiles. Regression analysis estimated the strength of relationships between attitudes and frequency of use. Results: We identified five clusters: Cluster 1 used heroin concomitantly with alcohol and occasionally crack; Cluster 2 used heroin and crack cocaine daily; Cluster 3 used heroin daily and almost exclusively; Cluster 4 used heroin and marijuana daily; and Cluster 5 were part-time drug users. Drug use frequency was associated with liking and being anxious when drugs could not be obtained. High perceived availability of heroin and cocaine and low cost facilitated polydrug use. Conclusions: Understanding polydrug use clusters among heroin users is important for addressing the larger opioid epidemic. Users’ perceptions of a drug's availability and cost appeared to facilitate polydrug use and justify more detailed future research on drug access.