Prudential PLC ADR (PUK) had the highest return between 2009 and 2021 by a large-cap US stock when the return was < 400%, returning 398.1%.

ASSET	YEARS	% RETURN
Prudential PLC ADR (PUK)	2009-2021	398.11%
Biomarin Pharmaceutical (BMRN)	2009-2021	396.63%
Amgen (AMGN)	2009-2021	396.53%
PayPal (PYPL)	2009-2021	396.26%
General Dynamics (GD)	2009-2021	396.25%
Elbit Systems (ESLT)	2009-2021	393.19%
SAP SE ADR (SAP)	2009-2021	390.74%
Old Republic International (ORI)	2009-2021	390.15%
Genesis Healthcare (GEN)	2009-2021	389.24%
Willis Towers Watson (WTW)	2009-2021	388.1%
Cboe Global Markets (CBOE)	2009-2021	387.19%
Westinghouse Air Brake Technologies (WAB)	2009-2021	384.19%
Allstate (ALL)	2009-2021	383.77%
Laboratory Corporation of America (LH)	2009-2021	383.47%
Expeditors International of Washington (EXPD)	2009-2021	380.03%
Travelers Companies (TRV)	2009-2021	377.52%
Enterprise Products Partners (EPD)	2009-2021	377.5%
Everest (EG)	2009-2021	377.31%
International Paper (IP)	2009-2021	375.35%
Principal Financial (PFG)	2009-2021	374.17%
Bilibili (BILI)	2009-2021	373.47%
Berkshire Hathaway (BRK.A)	2009-2021	373.38%
CNA Financial (CNA)	2009-2021	372.67%
T-Mobile US (TMUS)	2009-2021	368.79%
PACCAR (PCAR)	2009-2021	368.4%

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