Applied Digital (APLD) had the highest return between 2020 and 2021 by a small-cap US stock, returning 58,094.4%.

ASSET	YEARS	% RETURN
Applied Digital (APLD)	2020-2021	58,094.44%
Accolade (ACCD)	2020-2021	4,692.73%
Novavax (NVAX)	2020-2021	3,485.71%
Celldex Therapeutics (CLDX)	2020-2021	1,625%
Bit Digital (BTBT)	2020-2021	1,500%
Standard Lithium (SLI)	2020-2021	1,419.52%
Bitfarms (BITF)	2020-2021	1,221.99%
NRx Pharmaceuticals (NRXPW)	2020-2021	1,101.3%
Hut 8 Corp Common Stock (HUT)	2020-2021	877.34%
Lithium Argentina (LAR)	2020-2021	804.34%
Plug Power (PLUG)	2020-2021	779.44%
Digital Turbine (APPS)	2020-2021	745.91%
Owens & Minor (OMI)	2020-2021	739.36%
Amark Preci (AMRK)	2020-2021	729.64%
Danaos (DAC)	2020-2021	727.69%
Real Brokerage (REAX)	2020-2021	711.17%
Atlanticus (ATLC)	2020-2021	701.35%
Sigma Lithium Resources (SGML)	2020-2021	700.77%
Intellia Therapeutics (NTLA)	2020-2021	699.46%
Fulgent Genetics (FLGT)	2020-2021	674.96%
P10 (PX)	2020-2021	630.28%
Centrus Energy (LEU)	2020-2021	625.44%
Clene (CLNNW)	2020-2021	618.97%
Byrna Technologies (BYRN)	2020-2021	602.63%
Alpha Metallurgical Resources (AMR)	2020-2021	577.58%

Small-cap stocks are treated as having a market cap between $300M and $2B.