Insmed (INSM) had the highest return between 1999 and 2000 by a large-cap US stock, returning 1,917.3%.

ASSET	YEARS	% RETURN
Insmed (INSM)	1999-2000	1,917.3%
Laboratory Corporation of America (LH)	1999-2000	1,180.09%
Qualcomm (QCOM)	1999-2000	1,153.86%
Check Point Software Technologies (CHKP)	1999-2000	1,061.41%
Ciena (CIEN)	1999-2000	969.96%
Suzano Papel e Celulose SA ADR (SUZ)	1999-2000	888.13%
Biogen (BIIB)	1999-2000	705.57%
Quest Diagnostics (DGX)	1999-2000	700%
NetApp (NTAP)	1999-2000	440.53%
Regeneron Pharmaceuticals (REGN)	1999-2000	403.79%
Adobe Systems (ADBE)	1999-2000	399.31%
Infosys Ltd ADR (INFY)	1999-2000	398.92%
VeriSign (VRSN)	1999-2000	391.51%
Vertex Pharmaceuticals (VRTX)	1999-2000	378.66%
Neurocrine Biosciences (NBIX)	1999-2000	373.21%
Qorvo (QRVO)	1999-2000	359.68%
Celestica (CLS)	1999-2000	337.28%
Logitech International (LOGI)	1999-2000	304.16%
Oracle (ORCL)	1999-2000	299.72%
Revvity (RVTY)	1999-2000	291.32%
Waters (WAT)	1999-2000	282.26%
Coherent (COHR)	1999-2000	279.69%
Corning (GLW)	1999-2000	258.18%
Teva Pharma Industries Ltd ADR (TEVA)	1999-2000	255.7%
SEI Investments (SEIC)	1999-2000	243.97%

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