Depression is one of the most common mental disorders in caregivers. Therefore, preventive interventions for this population are needed, especially for caregivers with subclinical symptoms of depression. However, no study to date has identified the characteristics of caregivers that help to predict who will or will not benefit from such a preventive intervention. This study aimed to identify moderators of response to intervention comparing problem solving and usual care in indicated prevention of depression among informal caregivers. A randomized controlled trial was conducted involving 173 participants who were allocated to the problem-solving intervention (n=89) or the usual-care control-group (n=84), with 12-months follow-up. Socio-demographic, care-related and clinical variables at baseline were analyzed as potential moderators of intervention response at 12-months follow-up. Age and emotional distress emerged as significant moderators. Those caregivers younger than 65 years and with higher emotional distress at baseline were more likely to benefit from the intervention than from usual care. Simultaneous consideration of multiple moderators found that intervention was indicated for 95.4% of the sample. Considering these moderators in clinical decision-making could contribute to matching treatments and health service users in a more personalized and effective way.