We aimed to investigate whether the alterations of time intervals and velocity–time integrals (VTIs) of ductus venosus (DV) Doppler flow could predict evolving twin-to-twin transfusion syndrome (TTTS) in monochorionic diamniotic (MD) twin pregnancies in the second trimester. DV Doppler waveforms of MD twin pregnancies were retrospectively analyzed. Time intervals and VTIs of the accelerating phase of S-wave (S1 and VTI-1), decelerating phase of S-wave (S2 and VTI-2) and phase of D-wave (D and VTI-diast) were measured in the recipient twins of TTTS and the larger twins of uncomplicated MD twins. Each parameter was normalized to total time intervals and VTIs. DV parameters of prerecipient twins in pre-TTTS conditions were analyzed. The pre-TTTS condition was defined as the condition within 2 weeks before when TTTS cases fulfilled the criteria. Both recipient twins in TTTS cases and prerecipient twins in pre-TTTS condition showed significantly shorter S1, longer S2, shorter D, smaller VTI-1, larger VTI-2 and smaller VTI-diast than did the larger twins in uncomplicated MD twins (p < .05). Receiver-operating characteristic curve analysis showed that VTI-2 had better performance, and VTI-2 >45.5% had 87.0% sensitivity, 90.9% specificity, 81.0% positive predictive value and 93.0% negative predictive value for detecting prerecipient twins. Recipient twins complicated with TTTS have characteristic alterations in time intervals and VTIs of DV Doppler flow, which is present even before fulfilling the TTTS criteria. Furthermore, VTI-2 >45.5% is a possible predictive parameter for TTTS in the second trimester.