Objective: To evaluate whether older first-time mothers (≥37 years) have higher rates of postpartum depression compared with younger first-time mothers, controlling for mode of conception and known risk factors for postpartum depression. Design: Prospective cohort study. Setting: Assisted reproductive technology (ART) clinics in two large Australian cities and public and private antenatal clinics and/or classes in the vicinity of ART clinics. Patient(s): Nulliparous women who had conceived spontaneously (n = 295) or through ART (n = 297) in three age-groups: younger, 20 to 30 years (n = 173); middle, 31 to 36 years (n = 214); and older, ≥37 years (n = 189). Intervention(s): Semistructured interviews and questionnaires. Main Outcome Measure(s): Major depressive disorder in the first 4 months after birth as assessed by structured diagnostic interview. Result(s): The study performed 592 complete pregnancy assessments and 541 postpartum assessments. The prevalence of major depressive disorder was 7.9%, at the lower end of community rates. Neither maternal age-group nor mode of conception was statistically significantly related to depression. Conclusion(s): Older first-time mothers, whether conceiving through ART or spontaneously, do not show increased vulnerability to postnatal depression.