BackgroundPrimary care is the ideal setting for promotion and prevention intervention. Multiple risk behaviour interventions present several advantages over single-risk lifestyle interventions. Multiple risk behaviour interventions could be easily implemented in primary care to prevent non-communicable disease and depression.AimTo test the effectiveness of a multiple risk behaviour intervention to promote Mediterranean diet, physical activity, and/or smoking cessation in people attending Spanish primary health care with incidence of depression and symptoms of depression.MethodThis was a secondary analysis of the EIRA study that aims to test the effectiveness of a multiple risk behaviour intervention to promote healthy lifestyles. Twenty-six primary care centres were randomised to receive multiple risk behaviour intervention or usual care. The multiple risk behaviour intervention included individual sessions, group sessions, communitarian activities, and SMS reception. Participants were followed for 10–14 months. The primary outcomes of this study were incidence of depression and reductions of depressive symptoms.ResultsThree thousand and sixty-seven participants were included. Females accounted for 45.13% and 93.88% were Spanish. Age varied between 45 and 75 years old. The effectiveness of the intervention will be calculated using the Patient Health Questionnaire (PHQ-9) and the Composite International Diagnostic Interview (‎CIDI)‎ depression section. Linear and logistic regression will be used to create predictive models.ConclusionPrimary care is the most accessible service in the health system for patients. Hence primary care is the ideal setting for health education, promotion, and prevention interventions. This study will provide high-quality evidence about the effectiveness of multiple risk behaviour interventions over depression prevention.