| 1 | SANFORD | SIOUX FALLS | $6.1B | $4.3B | Unclassified |
| 2 | AVERA MCKENNAN | SIOUX FALLS | $1.7B | $1.8B | Health Care |
| 3 | SIGNATRY CHARITABLE TRUST | SIOUX FALLS | $1.0B | $816.2M | Philanthropy, Voluntarism & Grantmaking Foundations |
| 4 | MONUMENT HEALTH RAPID CITY HOSPITAL INC | RAPID CITY | $1.0B | $1.4B | Health Care |
| 5 | THE EVANGELICAL LUTHERAN GOOD SAMARITAN SOCIETY | SIOUX FALLS | $1.0B | $970.4M | Human Services |
| 6 | MARGOT AND TOM PRITZKER FOUNDATION | SIOUX FALLS | $423.3M | $449.6M | Philanthropy, Voluntarism & Grantmaking Foundations |
| 7 | EAST RIVER ELECTRIC POWER COOPERATIVE INC | MADISON | $371.4M | $1.0B | Unclassified |
| 8 | AVERA HEALTH PLANS INC | SIOUX FALLS | $307.1M | $97.1M | Health Care |
| 9 | AVERA HEALTH | SIOUX FALLS | $278.4M | $2.3B | Health Care |
| 10 | MONUMENT HEALTH NETWORK INC | RAPID CITY | $220.0M | $160.9M | Health Care |
| 11 | SANFORD HEALTH FOUNDATION | SIOUX FALLS | $214.4M | $1.3B | Philanthropy, Voluntarism & Grantmaking Foundations |
| 12 | AVERA ST LUKES | ABERDEEN | $197.1M | $150.1M | Health Care |
| 13 | PRAIRIE LAKES HEALTH CARE SYSTEM INC | WATERTOWN | $161.9M | $441.1M | Health Care |
| 14 | SACRED HEART HEALTH SERVICES | YANKTON | $156.8M | $429.2M | Health Care |
| 15 | AVERA QUEEN OF PEACE | MITCHELL | $142.6M | $180.6M | Health Care |
| 16 | GREAT PLAINS TRIBAL LEADERS HEALTH BOARD | RAPID CITY | $127.1M | $195.5M | Mental Health & Crisis Intervention |
| 17 | AUGUSTANA UNIVERSITY ASSOCIATION | SIOUX FALLS | $123.9M | $361.9M | Education |
| 18 | AVERA ST MARYS | PIERRE | $122.1M | $98.1M | Health Care |
| 19 | DELTA DENTAL OF SOUTH DAKOTA | PIERRE | $110.7M | $45.1M | Unclassified |
| 20 | SIOUX VALLEY-SOUTHWESTERN ELECTRIC COOPERATIVE INC | COLMAN | $108.1M | $384.7M | Unclassified |
| 21 | SIOUX FALLS AREA COMMUNITY FOUNDATION INC | SIOUX FALLS | $106.8M | $364.5M | Philanthropy, Voluntarism & Grantmaking Foundations |
| 22 | SOUTHEASTERN ELECTRIC COOPERATIVE INC | LENNOX | $87.6M | $265.1M | Mutual & Membership Benefit |
| 23 | AVERA AT HOME | SIOUX FALLS | $83.2M | $41.5M | Health Care |
| 24 | SOUTH DAKOTA STATE UNIVERSITY FOUNDATION | BROOKINGS | $73.3M | $411.9M | Education |
| 25 | RURAL HEALTH CARE INC | FT PIERRE | $65.9M | $29.6M | Unclassified |
| 26 | SOUTH DAKOTA COMMUNITY FOUNDATION | PIERRE | $60.1M | $939.2M | Philanthropy, Voluntarism & Grantmaking Foundations |
| 27 | HURON REGIONAL MEDICAL CENTER INC | HURON | $55.2M | $114.0M | Health Care |
| 28 | BLACK HILLS WORKS INC | RAPID CITY | $50.1M | $25.2M | Employment |
| 29 | OGLALA LAKOTA COLLEGE | KYLE | $49.6M | $144.2M | Education |
| 30 | LEWIS AND CLARK RURAL WATER SYSTEM INC | TEA | $49.2M | $595.8M | Public & Societal Benefit |
| 31 | WEST RIVER ELECTRIC ASSOCIATION INC | WALL | $49.0M | $179.3M | Unclassified |
| 32 | CHILDRENS CARE HOSPITAL & SCHOOL | SIOUX FALLS | $46.6M | $43.1M | Unclassified |
| 33 | SOUTH DAKOTA ACHIEVE | SIOUX FALLS | $43.7M | $28.1M | Human Services |
| 34 | UNIVERSITY OF SIOUX FALLS | SIOUX FALLS | $41.1M | $96.4M | Education |
| 35 | CENTRAL ELECTRIC COOPERATIVE INC | MITCHELL | $39.9M | $126.6M | Food, Agriculture & Nutrition |
| 36 | OGLALA LAKOTA HOUSING AUTHORITY | PINE RIDGE | $38.3M | $81.5M | Housing & Shelter |
| 37 | UNIVERSITY OF SOUTH DAKOTA FOUNDATION | VERMILLION | $38.2M | $367.5M | Education |
| 38 | MADISON COMMUNITY HOSPITAL | MADISON | $37.3M | $59.3M | Health Care |
| 39 | CHILDRENS HOME SOCIETY OF SOUTH DAKOTA | SIOUX FALLS | $35.3M | $58.2M | Human Services |
| 40 | SANFORD | SIOUX FALLS | $35.2M | $792.7M | Health Care |
| 41 | MOUNT MARTY UNIVERSITY | YANKTON | $34.7M | $76.4M | Education |
| 42 | HORIZON HEALTH CARE INC | HOWARD | $34.3M | $25.7M | Health Care |
| 43 | ASSOCIATION OF HUTTERIAN BRETHREN CHURCHES INC | ABERDEEN | $33.6M | $30.5M | Unclassified |
| 44 | FALL RIVER HEALTH SERVICES | HOT SPRINGS | $33.1M | $40.8M | Health Care |
| 45 | ST BENEDICT HEALTH CENTER | PARKSTON | $32.8M | $91.1M | Health Care |
| 46 | PRESBYTERIAN RETIREMENT VILLAGE OF RAPID CITY INC | RAPID CITY | $32.2M | $147.4M | Unclassified |
| 47 | FEEDING SOUTH DAKOTA | SIOUX FALLS | $32.2M | $22.9M | Food, Agriculture & Nutrition |
| 48 | NORTHERN ELECTRIC COOPERATIVE INCORPORATED | BATH | $31.4M | $117.4M | Unclassified |
| 49 | HEGG MEMORIAL HOSPITAL | SIOUX FALLS | $30.7M | $58.7M | Health Care |
| 50 | OAHE ELECTRIC COOPERATIVE INC | BLUNT | $30.0M | $42.8M | Unclassified |