This study investigates the trend of spatial distribution and characteristics of ketamine users in China during 2010–2015 based on China's National Surveillance System on Drug Abuse (NSSDA). A total of 28,670 ketamine users registered during the study period, and reported cases increased from 3192 in 2010 to 6878 in 2014, and dropped back to 4895 in 2015 (APC = 13.9, 95% CI: − 0.3 to 30.1, p = 0.1). Spatial distribution analyses at provincial level showed that regions with high report rate were clustered in southern China around Guangdong, and trends of spread into inland areas were observed. The proportion of new users, which reflected the relative growth of ketamine prevalence, increased from 6.27 to 12.34% over the study period (p < 0.001). Besides, the odds of being new users were higher among migrant users (also known as "floating population" in China) compared with local registered users. Our study verifies a significant association between floating population and ketamine spread, which calls for further investigation. [ABSTRACT FROM AUTHOR]