Key PointsQuestionIs an immediate, activated referral to care or a brief problem-solving intervention more effective for the initial management of screen-detected depression in pregnant and postpartum persons?FindingsIn this randomized clinical trial of 230 pregnant and postpartum participants followed up for 12 months, there were no significant differences in the rate of depressive or anxiety symptom episodes between groups; however, the evidence suggested improved symptom trajectory following immediate referral.MeaningFurther work is necessary to guide approaches to ensuring adequate follow-up care following a positive depression screen result among peripartum persons.