Introduction: Analyzing the situation and risk factors associated with using new psychoactive substances (NPS) is essential for preventing and controlling health consequences. This study explored the prevalence and associated factors of NPS use in the Thai population. Methods: This descriptive study was conducted in participants (N=30,411, mean age=42.4±13.4years, range=15–64years, 50.3% women) from urban and rural areas of Thailand. The participants were chosen using multistage sampling for large populations. The data were collected in July–December 2016 and analyzed using frequency, percentage, mean, standard deviation, chi-square, multiple logistic regression, and odds ratio with 95% confidence intervals (CI). Results: The prevalence of lifetime NPS use was 49.7% (95% CI, 49.1–51.3), past-year use was 31.3% (95% CI, 30.8–31.8), and current (past-month) use was 14.9% (95% CI, 14.5–15.3). Among current users, 29.5% were habitual users (over 20days). The factors associated with current NPS use were sex (male/female) (adjusted odds ratio [AOR]=1.145; 95% CI, 1.075–1.221; p<0.001), age group (25–64/15–24years) (AOR=1.126; 95% CI, 1.090–1.358; p<0.001), educational attainment (elementary or secondary education and higher) (AOR=1.634; 95% CI, 1.529–1.747; p<0.001), and employment status (AOR=1.842; 95% CI, 1.683–2.016; p<0.001). Conclusions: The prevalence of NPS use in Thailand is high, which reflects abuse behavior that could potentially harm users. Understanding the prevalence and risk factors of NPS use could benefit policymakers. Keywords: Factor, New psychoactive substance, Prevalence, Thailand