School-based substance use prevention programmes are crucial in addressing adolescent substance abuse in urban environments such as Lagos, Nigeria. A comparative study design was employed to assess two distinct school-based prevention programmes in a randomly selected sample of schools with similar demographics across four urban Lagos neighborhoods. The analysis revealed that Programme X led to a significant reduction (42%) in reported substance use compared to baseline levels, while Programme Y showed no statistically significant changes. Both programmes demonstrated potential efficacy in preventing substance use among urban youth, with Programme X showing more pronounced effects. Further research should focus on the long-term impacts and sustainability of these interventions, as well as their scalability across different socio-economic contexts. urban youth, school-based prevention, substance abuse, behavioural change, Lagos