AbstractElevated circulating insulin‐like growth factor‐1 (IGF‐1), a breast epithelial cell mitogen, is associated with breast cancer development. However, its association with breast cancer survival is not established. Circulating concentrations of IGF‐1 are controlledviabinding proteins, including IGF Binding Protein‐3 (IGFBP‐3), that may modulate the association of IGF‐1 with breast‐cancer outcomes. We measured IGF‐1 and IGFBP‐3 concentrations in serum from 600 women enrolled in the health, eating, activity, and lifestyle (HEAL) study, a multiethnic, prospective cohort study of women diagnosed with stage I‐IIIA breast cancer. We evaluated the association between IGF‐1 and IGFBP‐3, and as a ratio, modeled using quintile cut‐points, with risk of breast cancer‐specific (n= 42 deaths) and all‐cause mortality (n= 87 deaths) using Cox proportional hazards models. In models adjusted for body mass index, ethnicity, tamoxifen use at time of blood draw, treatment received at diagnosis and IGFBP‐3, women in the highest quintile of IGF‐1 level had an increased risk of all‐cause mortality (Hazard Ratio (HR) = 3.10, 95% CI 1.21–7.93,p= 0.02), although no dose‐response association was evident. The IGF‐1/IGFBP‐3 ratio, an indicator of free IGF‐I levels, was significantly associated with increasing risk of all‐cause mortality (HR = 2.83, 95% CI 1.25–6.36ptrend= 0.01, uppervs. lower quintile) in a fully adjusted model. In conclusion, high serum levels of IGF‐1 and the IGF‐1/IGFBP‐3 ratio were associated with increased risk of all‐cause mortality in women with breast cancer. These results need to be confirmed in larger breast cancer survivor cohorts.