InterContinental Hotels Group PLC ADR (IHG) had the highest return between 2000 and 2010 by a large-cap US stock, returning 14,004,900%.

ASSET	YEARS	% RETURN
InterContinental Hotels Group PLC ADR (IHG)	2000-2010	14,004,900%
National Grid PLC ADR (NGG)	2000-2010	1,128,370.59%
Natwest (NWG)	2000-2010	774,270%
Ferguson (FERG)	2000-2010	431,485.11%
Monster Beverage (MNST)	2000-2010	9,668.39%
Deckers Outdoor (DECK)	2000-2010	9,015.23%
Clean Harbors (CLH)	2000-2010	6,798.59%
Ambev SA ADR (ABEV)	2000-2010	3,928.28%
Southern Copper (SCCO)	2000-2010	3,375.41%
Altria (MO)	2000-2010	3,341.68%
Vale SA ADR (VALE)	2000-2010	2,679.2%
Alamos Gold (AGI)	2000-2010	2,357.84%
Tractor Supply (TSCO)	2000-2010	2,334.06%
Tapestry (TPR)	2000-2010	2,156.52%
Netflix (NFLX)	2000-2010	2,070.53%
Grupo Cibest (CIB)	2000-2010	1,966.42%
Sociedad Quimica y Minera de Chile SA ADR B (SQM)	2000-2010	1,754.21%
Chunghwa Telecom (CHT)	2000-2010	1,747.21%
Tenaris SA ADR (TS)	2000-2010	1,734.53%
Cameco (CCJ)	2000-2010	1,673.48%
Teck Resources Ltd Class B (TECK)	2000-2010	1,613.28%
Royal Gold (RGLD)	2000-2010	1,564.64%
Cognizant Technology Solutions Corp Class A (CTSH)	2000-2010	1,495.44%
Old Dominion Freight Line (ODFL)	2000-2010	1,406.47%
Baidu (BIDU)	2000-2010	1,362.58%

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