PURPOSE: Children of mothers with prenatal depression have elevated risk for depression later in life. Pregnant women are hesitant to use antidepressants due to fear of adverse fetal effects. To inform prevention, this study examined associations between maternal prenatal depression and antidepressant use, and adolescent depressive symptoms and suicidality. PATIENTS AND METHODS: Prospective data from 74,695 mother-adolescent dyads from the Kaiser Permanente Northern California integrated healthcare delivery system were used. Three prenatal exposure groups were examined: maternal depression and antidepressants (Med); depression and no antidepressants (No-Med); neither depression nor antidepressants (NDNM). Adolescent depressive symptoms (Patient Health Questionnaire-2 score ≥3) and suicidality were assessed for 12- to 18-year-olds. Associations were analyzed using mixed effects logistic regression, adjusted for confounders. RESULTS: Maternal prenatal depression was associated with higher odds of adolescent depressive symptoms (Med odds ratio [OR]: 1.50, 95% confidence interval [CI]: 1.23-1.84; No-Med OR: 1.59, CI: 1.34-1.88) and suicidality (Med OR: 2.36, CI: 1.67-3.34; No-Med OR: 1.54, CI: 1.10-2.14) compared to no prenatal depression (NDNM). Adolescents exposed to prenatal depression and antidepressants were not at greater odds of depressive symptoms (Med OR: 0.95, CI: 0.74-1.21) compared to those not exposed to antidepressants (No-Med). However, they showed non-significant but greater odds of suicidality (Med OR: 1.54, CI: 0.99-2.39). CONCLUSION: Our findings suggest that maternal prenatal depression is associated with adolescent depressive symptoms and suicidality, and that exposure to antidepressants in utero does not increase risk of depressive symptoms, specifically. While not statistically significant, the increased odds of suicidality among adolescents exposed to antidepressants suggest a possible association; however, further investigation is needed. After replication, the findings of this study may inform shared clinical decision-making when considering options regarding antidepressant use for the treatment of maternal prenatal depression.