BACKGROUND: Studies on electronic nicotine delivery systems (ENDS) often report data on the use of one device. However, people who use ENDS may use more than one device. Little is known about the prevalence of multiple device use among adults. METHODS: 1290 U.S. adults (21 +) using ENDS 5 + days/week completed the Wave 5 (February-April 2023) VAPER study survey, reported their device usage, and submitted photos of their most used ENDS device and liquid. We examined multiple device use and its association with cigarette smoking status, co-use of multiple substances, and characteristics of participants' most commonly used device and liquid using Rao-Scott chi-square tests and ANOVAs. RESULTS: 45.3 % of participants used multiple devices (two 27.9 %, three 12.7 %, four+ 4.7 %). Compared to single device use, participants who used multiple devices were more likely to currently smoke cigarettes (two 32.5 % vs. three+ 44.0 % vs. one 22.4 %, p <
0.0001), use multiple nicotine products and cannabis in the past 30 days (two 28.3 % vs. three+ 37.4 % vs. one 17.7 %, p <
0.0001), use disposable devices (salt, no adjustable settings) (two 44.3 % vs. three+ 56.5 % vs. one 20.4 %, p <
0.0001) and nicotine salt liquid (two 70.2 % vs. three+ 77.3 % vs. one 58.9 %, p <
0.0001). CONCLUSIONS: About half of adults frequently using ENDS used more than one device. Multiple device use was associated with current cigarette smoking, multiple substance use, and use of disposable devices as their most commonly used ENDS. Understanding multiple ENDS device use can help contextualize real-world use and inform potential benefits and unintended consequences of future regulations.