Several studies have revealed alarming rates of substance abuse in student population in the country. Industrialization, urbanization and increased exposure to Western life style in this country has contributed to the spread of substance use, from alcohol and tobacco acting as "gateway drugs" to the use of other substances like cocaine, heroin, amphetamine, inhalants and hallucinogens. This study was conducted to assess the use of a wide variety of psychoactive substances among medical students of Ambrose Ali University, Ekpoma, Edo state. The prevalence, pattern and sociodemographic factors associated with psychoactive substance use was determined. The modified student drug use questionnaire by WHO was used for the study. The sample consisted of 65% males, and 83% were Christians. Majority of the students are from the south- south geopolitical zone of Nigeria where the school is located. The age of respondents ranged from 17 – 42 years. The mean age was 23.8years with a standard deviation of 3.29years. The findings of this study showed that; the age at first use of psychoactive substances was less than 10 years; and the lifetime use of these substances ranged from 15.9% for tobacco, 62.1% for alcohol, 6.8% for tranquilizers,5.7% for cannabis, 5.7% for amphetamine, 2.7% for opioids and 1.7% for sedatives. Current use prevalence was 21.1% for alcohol, 3.0% for cigarette, 1.4% for cannabis, 0.5% for amphetamine, 1.1% for sedatives and 1.1% for opioids . In addition, more males were found to consume alcohol, tobacco and cannabis than females. Clinical medical students were significantly more previous year users of tobacco and lifetime users of tranquilizer. Alcohol use was significantly higher for life time use and previous year use in respondents whose mothers drank alcohol. The use of cocaine and heroine was not found among the medical students. The majority of users alcohol and tobaccco are experimenters and occasional users. From the findings above, there is the urgent need to design and implement programmes aimed at education, prevention and control of substance use and abuse among university students.