The present study was carried out in the most populated city in Northern Nigeria that is believed to have the highest number of commercial motorcyclists and highest prevalence of psychoactive substance use in the country. Research on psychoactive substance use among motorcycle operators in Northern Nigeria is limited, despite the high level of morbidity these substances cause to them. This study aimed to study the prevalence of psychoactive substance use among motorcycle operators in Kano, North western Nigeria. The study was cross-sectional descriptive. Participants for the study were commercial motorcyclists registered with the local branch of Amalgamated Commercial Motorcycle Owner's and Riders Association of Nigeria (ACOMORAN). Assessment was carried out with the use of socio-demographic questionnaire and World Health Organization Student Drug Use Questionnaire (SDUQ). Data obtained was analysed using Statistical Package for Social Sciences (SPSS), 17 th edition. Three hundred and ninety four (394) subjects participated in the study. The results showed that the prevalence of overall psychoactive substance use was 19.3%. The prevalence of tobacco, stimulant (gadagi), and cannabis use were 19.3, 11.9 and 3.8% respectively, while the prevalence of inhalants and opiates use were 2.0 and 1.3%, respectively. There were no reported use of alcohol, benzodiazepines and cocaine. All the subjects were males, Moslems, within the age range of 22 and 60 years mean of 32.7 ± 6.6 years. They were mostly married (88.6%), and more than two third of them (70.1%) were from Kano. The study has highlighted the prevalence of substance use among commercial motorcyclists. It has important implication for policy makers to initiate primary preventive measures that could be focused towards the reduction of substance use among commercial motorcyclists in the community.