Background: Drug-related deaths in the US continue to increase. Sentinel surveillance of high-risk populations can provide early warning for shifts in trends. Nightclub/festival attendees have high levels of drug use, so we explored whether use among this population can serve as a potential bellwether or indicator for use-related mortality in the general population.Methods: Trends in past-year cocaine and methamphetamine use were estimated from nightclub/festival attendees in New York City (NYC) and among NY residents, and trends were estimated for related death rates in NYC (2014/15-2019/20). Using national data from England and Wales (2010-2019), trends in past-year cocaine and ecstasy use (among the full population and among nightclub attendees) and related deaths were also estimated.Results: In NY/NYC, cocaine use remained stable in the general population, but use among nightclub/festival attendees and cocaine-related deaths doubled. Methamphetamine use among nightclub/festival attendees and death rates also more than doubled while use among the general population remained stable. In UK countries, increases in cocaine and ecstasy use were larger for infrequent/frequent nightclub attendees than in the general population, with 3.6- and 8-fold increases in related deaths, respectively. In UK countries, the association between nightclub attendance and death rates increased in a dose-response-like manner with larger associations detected when death rates were lagged by one year.Conclusions: Patterns of use among nightclub/festival attendees, more so than patterns in the general population, were similar to patterns of drug-related deaths. Use among this subpopulation could possibly serve as a bellwether for use-related outcomes. Continued surveillance is recommended.