InterContinental Hotels Group PLC ADR (IHG) had the highest return between 2000 and 2008 by a large-cap US stock, returning 5,519,600%.

ASSET	YEARS	% RETURN
InterContinental Hotels Group PLC ADR (IHG)	2000-2008	5,519,600%
National Grid PLC ADR (NGG)	2000-2008	1,018,952.94%
Natwest (NWG)	2000-2008	953,400%
Monster Beverage (MNST)	2000-2008	6,165.02%
Clean Harbors (CLH)	2000-2008	5,105.12%
Deckers Outdoor (DECK)	2000-2008	2,943.35%
Altria (MO)	2000-2008	1,731.07%
Banco Bradesco SA ADR (BBD)	2000-2008	1,695.66%
Sterling Construction (STRL)	2000-2008	1,382.4%
Royal Gold (RGLD)	2000-2008	1,380.38%
Gilead Sciences (GILD)	2000-2008	1,332.29%
Chunghwa Telecom (CHT)	2000-2008	996.6%
Southern Copper (SCCO)	2000-2008	967.8%
Ambev SA ADR (ABEV)	2000-2008	920.24%
NVR (NVR)	2000-2008	855.5%
Stifel Financial (SF)	2000-2008	852.22%
Vale SA ADR (VALE)	2000-2008	834.5%
Axon Enterprise (AXON)	2000-2008	805.19%
Tractor Supply (TSCO)	2000-2008	799.7%
Hologic (HOLX)	2000-2008	799.39%
Old Dominion Freight Line (ODFL)	2000-2008	793.49%
Elbit Systems (ESLT)	2000-2008	777.67%
Alamos Gold (AGI)	2000-2008	774.41%
BlackRock (BLK)	2000-2008	736.1%
Tapestry (TPR)	2000-2008	730.79%

Large-cap stocks are treated as having a market cap of $10B+.