Background: Symptoms of depression and anxiety are highly prevalent in adolescence and they are the cause of considerable suffering. Even so, adolescents are not inclined to seek professional help for emotional problems. Internet-based preventive interventions have been suggested as a feasible method of providing appropriate care to adolescents with internalizing symptoms. The objective of this study was to evaluate the effects of preventive Internet-based (guided) self-help problem-solving therapy (PST) for adolescents reporting mild to moderate symptoms of depression and/or anxiety as compared to a waiting list control group (WL). Methodology/Principal Findings: A total of 45 participants were randomized to the 2 conditions. PST consisted of 5 weekly lessons. Participants were supported by e-mail. Self-report measures of depression and anxiety were filled in at baseline and after 3 weeks, 5 weeks, and 4 months. Of the 45 participants, 28 (62.2%) completed questionnaires after 3 weeks, 28 (62.2%) after 5 weeks, and 27 (60%) after 4 months. Hierarchical linear modeling analyses revealed overall improvement over time for both groups on depressive and anxiety symptoms. However, no significant group x time interactions were found. No differences were found between completers and non-completers. Conclusions/Significance: Results show that depressive and anxiety symptoms declined in both groups. No support was found, however, for the assumption that Internet-based PST was efficacious in reducing depression and anxiety in comparison to the waiting list control group. This finding could represent lack of power. Trial Registration: Netherlands Trial Register NTR1322. © 2012 Hoek et al.