Insmed (INSM) had the highest return between 2000 and 2001 by a large-cap US stock, returning 1,188%.

ASSET	YEARS	% RETURN
Insmed (INSM)	2000-2001	1,188.02%
NVIDIA (NVDA)	2000-2001	466.48%
Quest Diagnostics (DGX)	2000-2001	365.46%
Laboratory Corporation of America (LH)	2000-2001	338.52%
NVR (NVR)	2000-2001	327.23%
CoreSite Realty (COR)	2000-2001	310.18%
Manhattan Associates (MANH)	2000-2001	277.65%
DaVita HealthCare Partners (DVA)	2000-2001	262.22%
CACI International (CACI)	2000-2001	249.08%
Altria (MO)	2000-2001	234.79%
Everest (EG)	2000-2001	213.27%
HF Sinclair (DINO)	2000-2001	207.84%
Penske Automotive (PAG)	2000-2001	192.88%
Enterprise Products Partners (EPD)	2000-2001	192.26%
Lennar (LEN)	2000-2001	191.57%
Brown & Brown (BRO)	2000-2001	190.87%
DR Horton (DHI)	2000-2001	189.88%
Encompass Health (EHC)	2000-2001	178.96%
Clean Harbors (CLH)	2000-2001	176.5%
UnitedHealth (UNH)	2000-2001	166.71%
Logitech International (LOGI)	2000-2001	161.36%
W R Berkley (WRB)	2000-2001	158.21%
Tenet Healthcare (THC)	2000-2001	155.43%
ResMed (RMD)	2000-2001	155.24%
Knight Transportation (KNX)	2000-2001	155.13%

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