Madrigal Pharmaceuticals (MDGL) had the highest return between 2016 and 2018 by a large-cap US stock, returning 875.9%.

ASSET	YEARS	% RETURN
Madrigal Pharmaceuticals (MDGL)	2016-2018	875.93%
EXACT Sciences (EXAS)	2016-2018	602.67%
Advanced Micro Devices (AMD)	2016-2018	566.43%
Teck Resources Ltd Class B (TECK)	2016-2018	509.76%
argenx NV ADR (ARGX)	2016-2018	436.7%
AXIA Energia (AXIA)	2016-2018	384.75%
BeiGene (ONC)	2016-2018	384.16%
Vale SA ADR (VALE)	2016-2018	355.09%
TKO (TKO)	2016-2018	352.63%
Block (XYZ)	2016-2018	339.92%
Texas Pacific Land Trust (TPL)	2016-2018	336.05%
NVIDIA (NVDA)	2016-2018	320.27%
Burlington Stores (BURL)	2016-2018	288.79%
Huazhu (HTHT)	2016-2018	282.16%
Twilio (TWLO)	2016-2018	272.24%
Exelixis (EXEL)	2016-2018	257.64%
NRG Energy (NRG)	2016-2018	253.28%
Kratos Defense & Security Solutions (KTOS)	2016-2018	247.9%
Banco Santander Brasil SA ADR (BSBR)	2016-2018	247.79%
Ascendis Pharma A-S (ASND)	2016-2018	246.9%
Leonardo DRS, Inc Common Stock (DRS)	2016-2018	239.51%
Five Below (FIVE)	2016-2018	225.24%
Align Technology (ALGN)	2016-2018	222.25%
Veeva Systems Inc Class A (VEEV)	2016-2018	214.84%
Ubiquiti Networks (UI)	2016-2018	213.03%

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