Loss of hand function after cervical spinal cord injury severely impairs functional independence. We describe a method for restoring volitional control of hand grasp in a subject with complete cervical quadriplegia (C5 ASIA Impairment Scale A) using a portable fully implanted brain-computer interface (BCI) within the home environment. The BCI consists of subdural surface electrodes placed over the dominant-hand motor cortex and connects to a transmitter implanted subcutaneously below the clavicle, which allows continuous reading of the electrocorticographic (ECoG) activity. Movement-intent was used to trigger functional electrical stimulation (FES) of the dominant hand during an initial 29-week laboratory study and subsequently via a mechanical hand orthosis during in-home use. Movement intent information could be decoded consistently throughout the 29-week in-laboratory study with a mean accuracy of 89.0% (range 78-93.3%). Improvements were observed in both the speed and accuracy of various upper extremity tasks, including lifting small objects and transferring objects to specific targets. After study week 23, the subject began to be able to extend his right thumb volitionally in the absence of the FES orthosis. At home decoding accuracy during open-loop trials reached an accuracy of 91.3% (range 80-98.95%) and an accuracy of 88.3% (range 77.6-95.5%) during closed-loop trials. A fully implanted BCI can be safely used to reliably decode movement intent from motor cortex, allowing for accurate volitional control of hand grasp and may potentially re-engage latent neural pathways to allow targeted re-innervation of muscles below the level of injury. (Funded by the Miami Project to Cure Paralysis; ClinicalTrials.gov number, NCT02564419.)