Early results of experimental human hand transplantation have been highly successful. At this date, published/presented reports indicate that 22 hands have been transplanted onto 17 recipients around the world. The first Louisville patient is currently the recipient of the longest surviving hand transplant in the world at 4 ½ years after surgery. Results of functional testing at 48-month follow up are presented. Motor return in the transplanted intrinsics confirmed by electrophysiologic testing reveals improvement over 3 year follow up results: Adductor pollicis (4/5), Abductor pollicis (3/5), first dorsal interosseous (2/5), and Lumbricals 3-4/FDM (4/5). Wrist dorsiflexion and ulnar deviation were 5/5; radial deviation and volarflexion were 4+/5. Grip strength at position II on Jamar dynamometer was 15 lb. Lateral pinch was 4.5 lb and two-point pinch was 1 lb. He can lift 60 pounds with both hands and 30 pounds with the transplanted hand. Carroll test score for upper extremity and global hand function was 62.5/99 (was 61/99 at 3 years). The list of tasks he can accomplish has improved including activities like tying shoelaces, dressing, turning book and newspaper pages, writing, throwing a ball, picking up checkers or poker chips and use both his hands in activities of daily living and his occupation. He is now undergoing therapy once every 2 weeks to improve hand strength and resistance. He can localize touch to the tips of thumb, long, ring and small fingers. Index is correct only 50% of the time. Two point discrimination: Static - 15 mm in index and small, >15 mm in thumb, long and ring (median and ulnar nerves). Moving - 15 mm in index and small, >15 mm in ring (median and ulnar nerves) and 14 mm in the thumb. Perceives hot and cold at fingertips. Can detect shapes with left hand and sweating still absent. Semmes-Weinstein monofilament scores at tips of fingers: thumb and index (3.22), long and small (3.61), ring (3.84). Maximum improvement was seen in the index (was 3.61 at 3 years). Tinel’s has continued to progress well and is maximum 5.5 cm distal to wrist crease. The second Louisville patient is now 29 months post-transplant. He has shown functional return similar to the first recipient at the same time point, despite presence of ongoing rejection that has been easily controlled with topical steroids or tacrolimus. Taken together, the transplant outcomes in our two patients mirror that of the world experience.