PURPOSE: Radiological follow-up of oncology patients requires the detection of metastatic lung lesions and the quantitative analysis of their changes in longitudinal imaging studies. Our aim was to evaluate SimU-Net, a novel deep learning method for the automatic analysis of metastatic lung lesions and their temporal changes in pairs of chest CT scans. MATERIALS AND METHODS: SimU-Net is a simultaneous multichannel 3D U-Net model trained on pairs of registered prior and current scans of a patient. It is part of a fully automatic pipeline for the detection, segmentation, matching, and classification of metastatic lung lesions in longitudinal chest CT scans. A data set of 5040 metastatic lung lesions in 344 pairs of 208 prior and current chest CT scans from 79 patients was used for training/validation (173 scans, 65 patients) and testing (35 scans, 14 patients) of a standalone 3D U-Net models and 3 simultaneous SimU-Net models. Outcome measures were the lesion detection and segmentation precision, recall, Dice score, average symmetric surface distance (ASSD), lesion matching, and classification of lesion changes from computed versus manual ground-truth annotations by an expert radiologist. RESULTS: SimU-Net achieved a mean lesion detection recall and precision of 0.93±0.13 and 0.79±0.24 and a mean lesion segmentation Dice and ASSD of 0.84±0.09 and 0.33±0.22 mm. These results outperformed the standalone 3D U-Net model by 9.4% in the recall, 2.4% in Dice, and 15.4% in ASSD, with a minor 3.6% decrease in precision. The SimU-Net pipeline achieved perfect precision and recall (1.0±0.0) for lesion matching and classification of lesion changes. CONCLUSIONS: Simultaneous deep learning analysis of metastatic lung lesions in prior and current chest CT scans with SimU-Net yields superior accuracy compared with individual analysis of each scan. Implementation of SimU-Net in the radiological workflow may enhance efficiency by automatically computing key metrics used to evaluate metastatic lung lesions and their temporal changes.