| 1 | Sanford Sioux Falls | Z | $6.1B | $6.1B | $4.3B |
| 2 | Avera McKennan Sioux Falls | E | $1.8B | $1.7B | $1.8B |
| 3 | Signatry Charitable Trust Sioux Falls | T | $1.4B | $1.0B | $816.2M |
| 4 | The Evangelical Lutheran Good Samaritan Society Sioux Falls | P | $1.2B | $1.0B | $970.4M |
| 5 | Monument Health Rapid City Hospital INC Rapid City | E | $1.0B | $1.0B | $1.4B |
| 6 | Prairie Lakes Health Care System INC Watertown | E | $604.1M | $161.9M | $441.1M |
| 7 | Sanford Health Foundation Sioux Falls | T | $474.3M | $214.4M | $1.3B |
| 8 | Margot and Tom Pritzker Foundation Sioux Falls | T | $423.8M | $423.3M | $449.6M |
| 9 | East River Electric Power Cooperative INC Madison | Z | $371.4M | $371.4M | $1.0B |
| 10 | Avera Health Plans INC Sioux Falls | E | $322.2M | $307.1M | $97.1M |
| 11 | Avera Health Sioux Falls | E | $278.9M | $278.4M | $2.3B |
| 12 | Monument Health Network INC Rapid City | E | $220.1M | $220.0M | $160.9M |
| 13 | Avera St. Lukes Aberdeen | E | $209.0M | $197.1M | $150.1M |
| 14 | Augustana University Association Sioux Falls | B | $157.6M | $123.9M | $361.9M |
| 15 | Sacred Heart Health Services Yankton | E | $157.1M | $156.8M | $429.2M |
| 16 | Sioux Falls Area Community Foundation INC Sioux Falls | T | $152.8M | $106.8M | $364.5M |
| 17 | Avera Queen of Peace Mitchell | E | $144.2M | $142.6M | $180.6M |
| 18 | University of South Dakota Foundation Vermillion | B | $136.7M | $38.2M | $367.5M |
| 19 | Sanford Sioux Falls | E | $135.5M | $35.2M | $792.7M |
| 20 | Great Plains Tribal Leaders Health Board Rapid City | F | $127.1M | $127.1M | $195.5M |
| 21 | Avera St. Marys Pierre | E | $124.2M | $122.1M | $98.1M |
| 22 | Delta Dental of South Dakota Pierre | Z | $114.3M | $110.7M | $45.1M |
| 23 | Sioux Valley-southwestern Electric Cooperative INC Colman | Z | $109.1M | $108.1M | $384.7M |
| 24 | Southeastern Electric Cooperative INC Lennox | Y | $88.2M | $87.6M | $265.1M |
| 25 | Rushmore Electric Power Cooperative INC Rapid City | Z | $84.8M | $11.0M | $79.2M |
| 26 | Childrens Home Foundation Sioux Falls | P | $84.7M | $16.7M | $179.1M |
| 27 | Avera at Home Sioux Falls | E | $83.2M | $83.2M | $41.5M |
| 28 | Presbyterian Retirement Village of Rapid City INC Rapid City | Z | $80.7M | $31.1M | $158.7M |
| 29 | South Dakota State University Foundation Brookings | B | $77.5M | $73.3M | $411.9M |
| 30 | Rural Health Care INC Ft Pierre | Z | $65.9M | $65.9M | $29.6M |
| 31 | South Dakota Community Foundation Pierre | T | $60.9M | $60.1M | $939.2M |
| 32 | Black Hills Works INC Rapid City | J | $57.7M | $50.1M | $25.2M |
| 33 | University of Sioux Falls Sioux Falls | B | $55.7M | $41.1M | $96.4M |
| 34 | Dakota State University Foundation Madison | B | $55.2M | $10.2M | $102.2M |
| 35 | Oglala Lakota College Kyle | B | $50.2M | $49.6M | $144.2M |
| 36 | West River Electric Association INC Wall | Z | $49.8M | $49.0M | $179.3M |
| 37 | Sdsm&t Center for Alumni Relations & Advancement Rapid City | B | $49.4M | $29.3M | $176.2M |
| 38 | Lewis and Clark Rural Water System INC Tea | W | $49.2M | $49.2M | $595.8M |
| 39 | Dow Rummel Village Sioux Falls | P | $48.3M | $26.2M | $71.7M |
| 40 | Childrens Care Hospital & School Sioux Falls | Z | $46.6M | $46.6M | $43.1M |
| 41 | Childrens Home Society of South Dakota Sioux Falls | P | $46.5M | $36.1M | $58.9M |
| 42 | Pine Rock Foundation INC Sioux Falls | Z | $45.4M | $0 | $98.1M |
| 43 | Lifescape Foundation Sioux Falls | E | $44.1M | $28.6M | $148.4M |
| 44 | South Dakota Achieve Sioux Falls | P | $43.7M | $43.7M | $28.1M |
| 45 | Central Electric Cooperative INC Mitchell | K | $41.8M | $39.9M | $126.6M |
| 46 | Mount Marty University Yankton | B | $39.7M | $34.7M | $76.4M |
| 47 | Oglala Lakota Housing Authority Pine Ridge | L | $38.3M | $38.3M | $81.5M |
| 48 | Madison Community Hospital Madison | E | $37.3M | $37.3M | $59.3M |
| 49 | Horizon Health Care INC Howard | E | $34.3M | $34.3M | $25.7M |
| 50 | Association of Hutterian Brethren Churches INC Aberdeen | Z | $33.6M | $33.6M | $30.5M |