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Background Recent substance abuse research indicates gender differences in the substance-related epidemiology, biological responses, progression to dependence, medical consequences and treatments. Studies exploring human sex-different responses to ketamine are rare and there has been no systemic survey of gender differences in ketamine use. Determining whether females are more susceptible than males to ketamine withdrawal symptoms and adverse effects is important, because it associated with treatment retention and outcome in drug users. Methods The Taiwanese juridical system has implemented a new regulation on ketamine in the year 2009. Ketamine users who are caught by the police, are mandated to attend an educational program. We recruited ketamine offenders from February 2010 to May 2012 at the Kunming branch of the Taipei City Hospital, where the educational classes are held. A designed questionnaire was performed to gather information about demographic characteristics, discontinuation symptoms, concomitant use of other substances, and subjective experience of memory impairment or urinary discomforts, and to compare the gender differences. Results A total of 1,614 ketamine users were surveyed and most of them were males (83.8%), with an average age of 26.3 ± 5.4 years. Female ketamine users presented significantly more discontinuation symptoms such as anxiety, dysphoria, and tremors compared with male users. 72.4% of total ketamine users smoked cigarettes concomitantly. Male ketamine users had a higher rate of concomitant betel nut use, while female ketamine users had a higher rate of concomitant hypnotic and alcohol use. 76% of total ketamine users reported cognitive impairment and 51.6% mentioned urinary symptoms. Furthermore, female ketamine users self-reported significantly greater levels of severity in cognitive impairment and urinary discomforts compared with male users. Less than 10% of total ketamine users in our study reported the desire to transfer for medical intervention or treatment, despite the high rates of discontinuation symptoms and negative physical side effects. Conclusions Gender differences were noted in the subjective experience of discontinuation symptoms, concomitant substance use, and severity of impairment related to ketamine use. However, the probable cause of the gender differences found in this study requires further investigation. We hoped our study will stimulate further research in this field.