Objective To analyze the screening significance of four-dimensional ultrasound time-space association imaging (STIC) combined with high-resolution flow imaging (HDF) for fetal heart valve disease (VHD). Methods:110 pregnant women suspected of having fetal VHD admitted to our hospital from January 2023 to October 2024 were selected as the research subjects. Two-dimensional ultrasound examination and STIC combined with HDF examination were respectively performed on the research subjects. Taking the follow-up results of delivery or induction of labor as the "gold standard" for diagnosing VHD, the diagnostic results of fetal VHD diagnosed by two-dimensional ultrasound examination and STIC combined with HDF examination were statistically analyzed. To analyze the diagnostic efficacy and predictive value of two-dimensional ultrasound examination and STIC combined with HDF examination in the diagnosis of fetal VHD. Compare the image acquisition time and the screening time of singleton fetuses of the two examination methods. Results: Among the 110 research subjects, 36 cases were confirmed positive and 74 cases were confirmed negative by the gold standard for diagnosis, respectively. The number of true positive and true negative cases detected by two-dimensional ultrasound was 27 and 58 respectively. The number of true positive and true negative cases detected by STIC combined with HDF was 34 and 67 respectively. The sensitivity of STIC combined with HDF examination in diagnosing fetal VHD was 94.44% (34/36), the specificity was 90.54% (67/74), and the accuracy was 91.82% (101/110), which were compared with those of two-dimensional ultrasound examination at 75.00% (27/36), 78.38% (58/74), and 77.27% (85/110). The missed diagnosis rate was 5.56% (2/36) and the misdiagnosis rate was 9.46% (7/74), which were lower than those of two-dimensional ultrasound examination at 25.00% (9/36) and 21.62% (16/74) respectively (P < 0.05). The positive predictive value of STIC combined with HDF examination in diagnosing fetal VHD was 82.93% (34/41), and the negative predictive value was 97.10% (67/69), which were higher than those of two-dimensional ultrasound examination at 62.79% (27/43) and 86.57% (58/67) (P < 0.05). Compared with two-dimensional ultrasound examination, the image acquisition time and single fetal screening time of STIC combined with HDF examination were significantly shortened (P < 0.05). Conclusion: STIC combined with HDF is used in prenatal screening for fetal VHD to improve the diagnostic sensitivity and accuracy. And it can shorten the image acquisition time and screening time.