| SANFORD GROUP RETURN | Sioux Falls | — | $5.7B | 26 |
| Avera McKennan | Sioux Falls | E20 Health Care | $1.5B | 17 |
| THE EVANGELICAL LUTHERAN GOOD SAMARITAN | Sioux Falls | P750 Human Services | $953.3M | 14 |
| Monument Health Rapid City Hospital Inc | Rapid City | E220 Health Care | $912.6M | 23 |
| EAST RIVER ELECTRIC POWER | Madison | — | $356.9M | 30 |
| AVERA HEALTH PLANS INC | Sioux Falls | E80 Health Care | $342.3M | 18 |
| Avera Health | Sioux Falls | E110 Health Care | $285.3M | 15 |
| SANFORD HEALTH FOUNDATION | Sioux Falls | T12 Philanthropy, Voluntarism & Grantmaking Foundations | $214.4M | 5 |
| Monument Health Network Inc | Rapid City | E22 Health Care | $210.7M | 18 |
| Avera St Luke's | Aberdeen | E22 Health Care | $200.1M | 11 |
| PRAIRIE LAKES HEALTH CARE SYSTEM INC | Watertown | E220 Health Care | $161.9M | 11 |
| Sacred Heart Health Services | Yankton | E220 Health Care | $148.4M | 9 |
| THE SIGNATRY CHARITABLE TRUST | Sioux Falls | T11 Philanthropy, Voluntarism & Grantmaking Foundations | $145.4M | 6 |
| Avera Queen of Peace | Mitchell | E220 Health Care | $133.5M | 11 |
| GREAT PLAINS TRIBAL LEADERS HEALTH | Rapid City | F99Z Mental Health & Crisis Intervention | $127.1M | 10 |
| AUGUSTANA UNIVERSITY ASSOCIATION | Sioux Falls | B420 Education | $123.9M | 7 |
| Avera St Mary's | Pierre | E220 Health Care | $108.7M | 13 |
| SIOUX FALLS AREA COMMUNITY | Sioux Falls | T310 Philanthropy, Voluntarism & Grantmaking Foundations | $106.8M | 3 |
| SIOUX VALLEY SOUTHWESTERN ELECTRIC | Colman | — | $106.1M | 18 |
| DELTA DENTAL OF SOUTH DAKOTA | Pierre | — | $103M | 27 |
| SOUTHEASTERN ELECTRIC COOPERATIVE INC | Lennox | Y22 Mutual & Membership Benefit | $87.6M | 17 |
| Avera at Home | Sioux Falls | E99Z Health Care | $76M | 17 |
| SOUTH DAKOTA STATE UNIVERSITY FOUNDATION | Brookings | B110 Education | $73.3M | 7 |
| SOUTH DAKOTA COMMUNITY FOUNDATION | Pierre | T30 Philanthropy, Voluntarism & Grantmaking Foundations | $69.2M | 5 |
| RURAL HEALTH CARE INC | Fort Pierre | — | $65.9M | 7 |
| HURON REGIONAL MEDICAL CENTER INC | Huron | E220 Health Care | $53.6M | 7 |
| OGLALA LAKOTA COLLEGE | Kyle | B43Z Education | $49.6M | 20 |
| BLACK HILLS WORKS INC | Rapid City | J300 Employment | $49.4M | 5 |
| LEWIS & CLARK RURAL WATER SYSTEM | Tea | W80Z Public & Societal Benefit | $49.2M | 1 |
| WEST RIVER ELECTRIC ASSN INC | Wall | — | $49M | 17 |
| UNIVERSITY OF SIOUX FALLS | Sioux Falls | B420 Education | $41.1M | 8 |
| CHILDREN'S CARE HOSPITAL AND SCHOOL | Sioux Falls | — | $41M | 6 |
| SOUTH DAKOTA ACHIEVE | Sioux Falls | P820 Human Services | $40.2M | 3 |
| CENTRAL ELECTRIC COOPERATIVE INC | Mitchell | K200 Food, Agriculture & Nutrition | $39.9M | 17 |
| Oglala Lakota Housing Authority | Pine Ridge | L20 Housing & Shelter | $38.3M | 0 |
| UNIVERSITY OF SOUTH DAKOTA FOUNDATION | Vermillion | B114 Education | $38.2M | 9 |
| MADISON COMMUNITY HOSPITAL | Madison | E220 Health Care | $37.3M | 7 |
| CHILDREN'S HOME SOCIETY OF SOUTH DAKOTA | Sioux Falls | P73Z Human Services | $35.3M | 6 |
| MOUNT MARTY UNIVERSITY | Yankton | B420 Education | $34.7M | 8 |
| HORIZON HEALTH CARE INC | Howard | E320 Health Care | $34.3M | 10 |
| Assn of Hutterian Brethren Churches | Aberdeen | — | $33.6M | 0 |
| FALL RIVER HEALTH SERVICES | Hot Springs | E21 Health Care | $33.1M | 7 |
| FEEDING SOUTH DAKOTA | Sioux Falls | K31 Food, Agriculture & Nutrition | $32.6M | 4 |
| MARGOT AND TOM PRITZKER FOUNDATION | Sioux Falls | T20 Philanthropy, Voluntarism & Grantmaking Foundations | $32.5M | 1 |
| PRESBYTERIAN RETIREMENT VILLAGE OF | Rapid City | — | $32.2M | 7 |
| NORTHERN ELECTRIC COOPERATIVE | Bath | — | $31.4M | 18 |
| St Benedict Health Center | Parkston | E22 Health Care | $30.2M | 9 |
| OAHE ELECTRIC COOPERATIVE INC | Blunt | — | $30M | 12 |
| MOBRIDGE REGIONAL HOSPITAL | Mobridge | E22 Health Care | $30M | 8 |
| DOW RUMMEL VILLAGE | Sioux Falls | P750 Human Services | $29.5M | 7 |
