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How to efficiently serve ever-larger trained natural language models in practice has become exceptionally challenging even for powerful cloud servers due to their prohibitive memory/computation requirements. In this work, we present an efficient and affordable post-training quantization approach to compress large Transformer-based models, termed as ZeroQuant. ZeroQuant is an end-to-end quantization and inference pipeline with three main components: (1) a fine-grained hardware-friendly quantization scheme for both weight and activations; (2) a novel affordable layer-by-layer knowledge distillation algorithm (LKD) even without the access to the original training data; (3) a highly-optimized quantization system backend support to remove the quantization/dequantization overhead. As such, we are able to show that: (1) ZeroQuant can reduce the precision for weights and activations to INT8 in a cost-free way for both BERT and GPT3-style models with minimal accuracy impact, which leads to up to 5.19x/4.16x speedup on those models compared to FP16 inference; (2) ZeroQuant plus LKD affordably quantize the weights in the fully-connected module to INT4 along with INT8 weights in the attention module and INT8 activations, resulting in 3x memory footprint reduction compared to the FP16 model; (3) ZeroQuant can be directly applied to two of the largest open-sourced language models, including GPT-J6B and GPT-NeoX20, for which our INT8 model achieves similar accuracy as the FP16 model but achieves up to 5.2x better efficiency.