The Club Drugs and Health Project was supported by a grant from the National Institute on Drug Abuse (R01-DA014925-02, Jeffrey T. Parsons, Principal Investigator). Christian Grov was supported as a postdoctoral fellow in the Behavioral Sciences training in drug abuse research program sponsored by Public Health Solutions and the National Development and Research Institutes, Inc. (NDRI) with funding from the National Institute on Drug Abuse (T32 DA07233). The authors recognize the contributions of the Club Drug and Health Project team-Michael Adams, Virginia Andersen, Anthony Bamonte, Jessica Colon, Armando Fuentes, Sarit A. Golub, Chris Hietikko, Eda Inan, Juline Koken, Jose E. Nanin, Anthony Surace, Julia Tomassilli, Jon Weiser, Brooke E. Wells, and the recruitment team. An earlier version of this paper was presented at the 2008 meeting of the College on Problems of Drug Dependence (CPDD). Though some researchers have indicated club drug users are more likely to be polydrug users, there remains little known about the prevalence and specific combinations of the substances they use. Between 2004 and 2006, and using time-space sampling, a stratified sample of 400, 18-29-year-old New York City club-going, drug-using young adults were recruited into the Club Drugs and Health Project. Most participants (91.7%) had engaged in polydrug usage and 1,670 combinations of drugs were reported. Ecstasy (86.6% of users) and cocaine (85.7% of users) were the two most-frequently reported club drugs used in combination with other substances. In terms of poly-club drug combinations, ecstasy appeared to be the "universal compliment" as this drug was most often cited in combinations with other club drugs (specifically ecstasy + ketamine, ecstasy + cocaine, ecstasy + gamma hydroxybutyrate or GHB). Other frequently cited drug combinations included cocaine and marijuana, ecstasy and marijuana, LSD and marijuana, and cocaine and alcohol. These data highlight the need to develop drug health-education and prevention messages targeted at polydrug usage.