BACKGROUND: This study aimed to investigate the role of a time-domain Heart Rate Variability index (the root mean square of successive difference between NN intervals, rMSSD) as a predictor of the onset of postpartum depression. HRV has been related to an increased risk of depression in the general population. However, its role in pregnant women is not clear, and the potential use of smartphone applications to evaluate HRV in this population has not been investigated. METHODS: In study 1, simultaneous electrocardiogram and smartphone photoplethysmography were collected. The rMSSD was determined from each recording to evaluate the accuracy of a smartphone application in the measurement of HRV. In study 2, 135 pregnant women provided rMSSD values measured through a smartphone application in the prepartum (second or third trimester) and filled in the Edinburgh Postnatal Depression Scale in the postpartum (one month after the childbirth). RESULTS: Study 1 showed the excellent accuracy of the smartphone application in the measurement of rMSSD. Study 2 indicated that lower prepartum rMSSD predicted higher depressive symptoms in the postpartum (beta = -0.217, p = 0.010) after controlling for prepartum depressive symptoms and other potential covariates. LIMITATIONS: Artefacts (e.g., hand movements) might have corrupted the physiological signal registered. CONCLUSION: This study showed that a reduced vagal tone, indexed by lower rMSSD, during pregnancy was a predictor of depressive symptoms one month after childbirth. The prepartum period may offer an important timeframe to implement preventive intervention on vagal modulation in order to prevent depressive symptoms in the postpartum.