Manhattan Associates (MANH) had the highest return between 2000 and 2000 by a US stock with a market cap of $5B+, returning 452.2%.

ASSET	YEARS	% RETURN
Manhattan Associates (MANH)	2000-2000	452.23%
Comstock Resources (CRK)	2000-2000	402.13%
Laboratory Corporation of America (LH)	2000-2000	377.23%
Quest Diagnostics (DGX)	2000-2000	360.85%
Vertex Pharmaceuticals (VRTX)	2000-2000	302.82%
Skechers (SKX)	2000-2000	300.02%
Meritage (MTH)	2000-2000	246.52%
CoreSite Realty (COR)	2000-2000	225.81%
EOG Resources (EOG)	2000-2000	219.43%
Everest (EG)	2000-2000	216.03%
Waters (WAT)	2000-2000	213.62%
Universal Health Services (UHS)	2000-2000	209.34%
Encompass Health (EHC)	2000-2000	207.06%
Sun Life Financial (SLF)	2000-2000	205.34%
SEI Investments (SEIC)	2000-2000	179.24%
Ciena (CIEN)	2000-2000	178.37%
Regeneron Pharmaceuticals (REGN)	2000-2000	167.42%
Check Point Software Technologies (CHKP)	2000-2000	160.61%
Manulife Financial (MFC)	2000-2000	159.31%
Altria (MO)	2000-2000	159.2%
NVR (NVR)	2000-2000	158.85%
Revvity (RVTY)	2000-2000	153.79%
DaVita HealthCare Partners (DVA)	2000-2000	153.7%
Chubb (CB)	2000-2000	153.03%
NOV (NOV)	2000-2000	148.6%