Nine spiral nerve cuff electrodes were implanted in two human subjects for up to three years with no adverse functional effects. The objective of this study was to look at the long term nerve and muscle response to stimulation through nerve cuff electrodes. The nerve conduction velocity remained within the clinically accepted range for the entire testing period. The stimulation thresholds stabilized after approximately 20 weeks. The variability in the activation over time was not different from muscle-based electrodes used in implanted functional electrical stimulation systems. Three electrodes had multiple, independent contacts to evaluate selective recruitment of muscles. A single muscle could be selectively activated from each electrode using single-contact stimulation and the selectivity was increased with the use of field steering techniques. The selectivity after three years was consistent with selectivity measured during the implant surgery. Nerve cuff electrodes are effective for chronic muscle activation and multichannel functional electrical stimulation in humans.