We analyzed individual and program characteristics associated with participation in an ICT-based substance use preventive intervention in Uruguay, South America. The intervention was directed at nine- and ten-grade students in ten private schools in Montevideo. Participation in the program was non-mandatory and effective participation rates were low. We found that individual characteristics, such as prior heavy engagement with alcohol and opportunity costs of time, were associated with the decision to participate. We also found that sending the participants periodic reminders via email and SMS text messages had a positive impact in participation. The lessons from this intervention suggest that participation in non mandatory web-based programs aimed at preventing substance use among adolescents could be substantially improved with a more structured, mandatory, and longer intervention.