The short-reach optical transmission systems based on intensity modulation and direct detection (IM/DD) are gradually evolving into the networks with complex link topologies and connections, especially inside the data center. Multipath interference (MPI) introduces irregular fluctuations in the 4-level pulse amplitude modulation (PAM4) signals and therefore affects the transmission performance. This Letter proposes an adaptive decision threshold (ADT) scheme to dynamically update the decision threshold, which can track the signal fluctuations in real time and mitigate the impact of MPI noise on the transmitted PAM4 signals. Numerical simulation results present that the proposed ADT scheme can significantly improve the bit error rate (BER) performance of the MPI-impaired PAM4 transmission system considering different MPI levels and laser linewidths. In a 50-Gbps PAM4 transmission system, the ADT can improve the MPI tolerance by more than beyond 6 dB when the BER reaches the KP4-forward error correction (FEC) criterion (2.4 × 10-4), presenting a better denoising performance than the existing MPI-mitigation algorithms A1 and A2. Moreover, the ADT scheme offers a lower computation complexity compared with A1 and A2, making it more practical for implementation.