Electronic dance music (EDM) party attendees are a high-risk population for drug use and associated adverse effects. We examined trends in past-year drug use within this population to better inform prevention and harm reduction efforts.Each summer from 2016 through 2019, we used time-space sampling to survey a cross-section of adults entering EDM parties at randomly selected nightclubs and at dance festivals in New York City. Ns ranged from 504 (2019) to 1,087 (2016). We estimated log-linear trends in past-year use of 16 different synthetic drugs or drug classes.Between 2016 and 2019, estimated past-year prevalence of use of ketamine increased from 5.9% to 15.3% (a 157.6% relative increase; P = .007), LSD use increased from 9.9% to 16.6% (a 67.7% relative increase, P < .001), powder cocaine use increased from 17.3% to 35.2% (a 103.5% relative increase, P < .001), and GHB use increased from 1.0% to 4.2% (a 311.8% relative increase; P = .002). Past-year use of >3 drugs increased from 12.7% to 20.5% (a 61.4% relative increase; P = .013); however, estimated past-year use of unknown powders decreased from 2.0% to 1.1% (a relative 44.7% decrease; P = .038) and ecstasy/MDMA/Molly use was stable across years (at 25.0 to 28.5 %; P = .687).Reports of powder cocaine, LSD, ketamine, and GHB are becoming more prevalent among EDM party attendees. Prevention and harm reduction efforts are needed to address increasing use. Research is also needed to examine whether increasing media coverage of medical use of ketamine and other psychedelics affects prevalence of recreational use.