Time-space sampling has been used to generate representative samples of both hard-to-reach and location-based populations. Because of its emphasis on multi-tiered randomization (i.e., time, space, and individual), some have questioned the feasibility of time-space sampling as a cost-effective strategy. In an effort to better understand issues related to drug use among club-going young adults (ages 18 to 29) in the New York City nightlife scene, two variations of time-space sampling methods were utilized and compared (Version 1: randomized venue, day, and individuals within venues: Version 2: randomized venue and day). A list of nightlife venues were randomized and survey teams approached potential participants as they entered or exited venues to conduct brief anonymous surveys. Over the course of 24 months, 18,169 approaches were conducted and 10,678 consented to complete the brief questionnaire (V1 response rate = 46.0%, V2 response rate = 62.5%). Drug use was fairly common, with nearly two-thirds of the sample reporting having ever tried an illegal drug and more than half of drug users specifically tried either MDMA/ecstasy and/or cocaine. There were few differences between young adults surveyed during Version 1 and Version 2. Time-space sampling is an effective strategy to quickly detect and screen club drug users. Although caution is urged, elimination of the third tier of randomization (i.e., individual level counting) from time-space sampling may significantly improve response rates while only minimally impacting sample characteristics.