Depressive disorders are highly prevalent in the working population and are associated with excessive costs. The evidence for effective worker-directed interventions for employees with depressive symptoms is limited. Treating employees with depressive symptoms via the Internet before they report sick from work could be beneficial and cost saving. Objective: In this study, we tested the effectiveness over the period of 1 year of a Web-based guided self-help intervention, called Happy@Work, for employees with depressive symptoms who were not on sick leave. Methods: A two-arm randomized controlled trial comparing a worker-directed, Web-based, guided self-help intervention to care as usual (CAU) was carried out. We recruited employees from 6 companies via the company's Intranet and by putting up posters. The inclusion criteria were elevated depressive symptoms as measured by a score ≥16 on the Center for Epidemiologic Studies Depression scale (CES-D) and not being on sick leave. The intervention contained 6 lessons and consisted of problem-solving treatment and cognitive therapy. Participants were asked to submit weekly assignments via the website after completion of a lesson and they received feedback from a coach via the website. Self-report questionnaires on depressive symptoms (CES-D; primary outcome), burnout (Maslach Burnout Inventory, MBI), work performance (Health and Work Performance Questionnaire, HPQ), duration of absenteeism, and anxiety (Hospital Anxiety and Depression Scale, HADS; secondary outcomes), were completed at baseline, posttreatment, and at 6-, and 12-month follow-up. Several subgroup and per-protocol analyses were performed. Results: A total of 231 employees were randomized to either the intervention group (n=116) or to CAU (n=115). Completion of assessments varied between 54%-74%. Improvement in depressive symptoms between baseline and posttreatment was shown in all participants and these effects sustained over time. However, there were no differences between the 2 groups (adjusted regression coefficient=0.46, 95% CI-2.11 to 3.03, P=.72; Cohen's d=0.05). Differences between groups were also not significant for the secondary outcomes. No subgroups were identified to show differences between the groups, nor did we find a between-group effect in the per-protocol analyses. Conclusions: This study showed that a worker-directed, Web-based, guided self-help intervention was not more effective than CAU in reducing depressive symptoms among employees with depressive symptoms who were not on sick leave over the period of 1 year. An intervention for this specific target group might not be necessary because the recovery in the CAU group was comparable to the intervention group and sustained over a 12-month period. Trial Registration: Nederlands Trial Register (NTR): NTR2993; http://www. trialregister.nl/trialreg/admin/rctview.asp?TC=2993 (Archived by WebCite at http://www.webcitation.org/6PL9pFC0n).