Substance abuse is causing increasing threats to the stability of young minds, from teenage to the older youths and is an issue of public health concern in Nigeria. This study was carried out to determine the prevalence of drug abuse among students of tertiary institutions in Ekiti State. A comparative cross-sectional survey was carried out among students in tertiary institutions in Ekiti state with participants selected from Year 1 to Year 4. Data collection tool was the WHO questionnaire (STASSIS). Data was analysed to obtain descriptive and inferential data, Kruskal-Wallis test and chi square were used for analysis of variance and test of association. The majority of the students reported low use of all the drugs (64-90.1%) though moderate to high use were reported for: alcohol 35.1%, marijuana 15.7%, heroine 15.3%, tobacco 13.8% and cocaine 10.2%. There was a significant association between student's moderate to high use and university type. Students in private universities reported more use, especially heroine. Difference in substance use across the four years surveyed was significant with final year students (400 level) showing highest use. Tertiary students in Ekiti state are low users of psychoactive substances with a prevalence of 60-91%. Moderate to high prevalence of 10-31% was reported with alcohol as the substance with highest usage. Substance use varied significantly with university type with highest prevalence in the private institution and students at different academic levels with final year students being the highest users. © 2021 The Author(s).