The intuitive control of upper-limb prostheses requires a man/machine interface that directly exploits biological signals. Here, we define and experimentally test an offline man/machine interface that takes advantage of the discharge timings of spinal motor neurons. The motor-neuron behaviour is identified by deconvolution of the electrical activity of muscles reinnervated by nerves of a missing limb in patients with amputation at the shoulder or humeral level. We mapped the series of motor-neuron discharges into control commands across multiple degrees of freedom via the offline application of direct proportional control, pattern recognition and musculoskeletal modelling. A series of experiments performed on six patients reveal that the man/machine interface has superior offline performance compared with conventional direct electromyographic control applied after targeted muscle innervation. The combination of surgical procedures, decoding and mapping into effective commands constitutes an interface with the output layers of the spinal cord circuitry that allows for the intuitive control of multiple degrees of freedom.