Abstract: The deep convolutional neural network U-net has been introduced into adaptive subtraction, which is a critical step in effectively suppressing seismic multiples. The U-net approach has higher precision than the traditional linear regression approach. However, the existing 2D U-net approach with 2D data windows can not deal with elaborate discrepancies between the actual and simulated multiples along the gather direction. It may lead to erroneous preservation of primaries or generate obvious vestigial multiples, especially in complex media. To further enhance the multiple suppression accuracy, we present an adaptive subtraction approach utilizing 3D U-net architecture, which can adaptively separate primaries and multiples utilizing 3D windows. The utilization of 3D windows allows for enhanced depiction of spatial continuity and anisotropy of seismic events along the gather direction in comparison to 2D windows. The 3D U-net approach with 3D windows can more effectively preserve the continuity of primaries and manage the complex disparities between the actual and simulated multiples. The proposed 3D U-net approach exhibits 1 dB improvement in the signal-to-noise ratio compared to the 2D U-net approach, as observed in the synthesis data section, and exhibits more outstanding performance in the preservation of primaries and removal of residual multiples in both synthesis and reality data sections. Moreover, to expedite network training in our proposed 3D U-net approach we employ the transfer learning (TL) strategy by utilizing the network parameters of 3D U-net estimated in the preceding data segment as the initial network parameters of 3D U-net for the subsequent data segment. In the reality data section, the 3D U-net approach incorporating TL reduces the computational expense by 70% compared to the one without TL.