BACKGROUND: Despite empirical evidence demonstrating the effectiveness of collaborative stepped care program (SCP) in Western countries, such programs have not been evaluated in the east, which has a different services system structure and cultural nuances in seeking help for mental illness. Furthermore, only a few studies have used SCP for depression and anxiety prevention. We conducted a trial to test its effectiveness in preventing major depressive disorder and generalized anxiety disorder among primary care patients with subthreshold depression and/or anxiety in Hong Kong. METHODS: Subthreshold depression and/or anxiety patients were randomized into the SCP group (n=121) or care as usual (CAU) group (n=119). The SCP included watchful waiting, telephone counseling, problem solving therapy, and family doctor treatment within one year. The primary outcome was the onset of major depressive disorder or generalized anxiety disorder in 15 months. The secondary outcomes were depressive and anxiety symptoms, quality of life and time absent from work due to any illness. RESULTS: Survival analysis showed no differences between the SCP and CAU groups (the cumulative probability of onset at 15 month was 23.1% in the SCP group and 20.5% in the CAU group; Hazard Ratio=1.62; 95% Confidence Interval: 0.82-3.18; p=0.16). No significant differences were found in secondary outcomes. LIMITATIONS: Sample size might not have been large enough. CONCLUSIONS: SCP did not show beneficial effect on depression/anxiety prevention compared with CAU in Hong Kong primary care. As a large majority of patients improved overtime without any intervention, we are not able to exclude the possibility that the intervention might be effective. Future studies would need to have a larger sample size and conduct on patients with more severe symptoms or perform a second screening.