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This paper reports a multi-channel neural spike recording system-on-chip (SoC) with digital data compression and wireless telemetry. The circuit (16 active channels plus 48 ”mute” lines) demonstrates the potentials of a 64-channel system made by a low-noise analog front-end, a single 8-bit SAR ADC, followed by digital signal compression and transmission units. The 400-MHz transmitter uses a Manchester-Coded Frequency Shift Keying (MC-FSK) with low modulation index. In this way a 1.25-Mbit/s data rate is delivered within a band of about 3MHz. Compression of the raw data is implemented by detecting the action potential (AP) spikes and storing up to 20 points for each waveform. The choice greatly improves data quality and allows single spike identification. The chip, fabricated in 0.35-μm CMOS AMS process, occupies a 3.1 × 2.7 mm2 area. A 4-m transmission range is reached with an overall power consumption of 16.6 mW. The figure translates into a power budget of 269 μW per channel for a complete 64-channel system, which favorably compares with the results in literature. The system performance has been verified in in-vivo neural recording experiments.