Huron-based turkey-processing cooperative formed in 2004 by Dakota Turkey Growers, largely Hutterite-colony farms; its $120 million plant processes roughly 8 million turkeys a year into raw and ready-to-eat products under the Dakota44 brand, employing about 925 people.

Volga-headquartered farmer-owned cooperative (~2,200 members) operating a soybean crush plant and oil refinery founded in 1993; processes locally grown soybeans into soybean meal and oil for livestock feed and food markets.

Sioux Falls-headquartered bank and credit-card issuer; together First PREMIER Bank and sister company PREMIER Bankcard rank among the largest issuers of Visa/Mastercard credit cards in the US, with more than 2,200 South Dakota employees. Founded 1986.

Sioux Falls-headquartered nonprofit regional health system operating hospitals, clinics, and senior-care facilities across South Dakota, Minnesota, Iowa, and Nebraska; among South Dakota's largest employers.

Rapid City-headquartered diversified energy holding company providing regulated electric and natural gas utility service to roughly 1.3 million customers across eight states. NYSE: BKH.

Citibank moved its credit-card operations to Sioux Falls in 1981 after South Dakota abolished interest-rate caps, founding the state's credit-card industry.

Brookings-headquartered manufacturer of large-scale digital video displays, scoreboards, digital billboards, and dynamic message signs, founded 1968; Daktronics boards appear in major sports stadiums, Times Square, and the Las Vegas Strip. Nasdaq: DAKT.

Sioux Falls-headquartered regional drugstore chain founded in 1942, operating roughly 59 stores across South Dakota, Minnesota, and Iowa; acquired by Sanford Health in 2025 while retaining its branding and employees.

Sioux Falls-headquartered electric and natural gas utility holding company serving South Dakota, Nebraska, and Montana; relocated its corporate headquarters to Sioux Falls. Nasdaq: NWE.

Sioux Falls-headquartered financial holding company (formerly Meta Financial Group / MetaBank) operating Pathward, N.A., a bank specializing in embedded finance, prepaid cards, tax-refund products, and commercial banking for fintech partners. Nasdaq: CASH.

Sioux Falls-headquartered biofuel producer and the world's largest ethanol producer, operating more than 30 ethanol plants across seven Midwest states and processing roughly 3 billion gallons of ethanol a year — about 19% of total US ethanol output. Founded by the Broin family.

Sioux Falls-founded (1956) precision-agriculture technology and engineered-films manufacturer serving agricultural, industrial, and aerospace customers; acquired by CNH Industrial in 2021 and continues to operate its precision-ag business from Sioux Falls.

Sioux Falls-headquartered nonprofit integrated health system and South Dakota's largest employer, with more than 47,000 employees operating hospitals and clinics across the Dakotas, Minnesota, Iowa, and beyond; acquired regional pharmacy chain Lewis Drug in 2025.

Underground physics laboratory in Lead, a mile beneath a former gold mine, hosting the LUX-ZEPLIN dark-matter experiment and the DUNE neutrino experiment excavation.

US Geological Survey center outside Sioux Falls housing the nation's Landsat satellite-imagery archive.