| LUTHERAN HOMES OF SOUTH CAROLINA INC | Irmo | P750 Human Services | $88.8M | 8 |
| LOWCOUNTRY FOOD BANK INC | Charleston | — | $87.5M | 5 |
| BLACK RIVER ELECTRIC | Sumter | — | $84M | 16 |
| FAIRFIELD ELECTRIC COOPERATIVE INC | Blythewood | — | $83.1M | 17 |
| MEDICAL UNIVERSITY OF SOUTH CAROLINA | Charleston | H90 Medical Research | $80.6M | 3 |
| MYRTLE BEACH AREA CHAMBER OF COMMERCE | Myrtle Beach | — | $80M | 9 |
| MCLEOD MEDICAL CENTER DILLON | Florence | E220 Health Care | $79.8M | 13 |
| MCLEOD HEALTH CHERAW | Florence | E20 Health Care | $78.8M | 11 |
| Presbyterian Communities of South Carolina | Columbia | P750 Human Services | $76.9M | 8 |
| EAU CLAIRE COOPERATIVE HEALTH | Columbia | — | $76.9M | 12 |
| CLEMSON UNIVERSITY FOUNDATION | Clemson | B11 Education | $75M | 4 |
| SOUTHERN MUTUAL CHURCH INSURANCE CO | Columbia | Y20Z Mutual & Membership Benefit | $73.8M | 15 |
| Farm Credit Benefits Alliance Employee | Columbia | Y43 Mutual & Membership Benefit | $73.4M | 1 |
| CARESOUTH CAROLINA INC | Hartsville | E320 Health Care | $73.2M | 9 |
| North Greenville University | Tigerville | B410 Education | $70.2M | 10 |
| BENEDICT COLLEGE | Columbia | B420 Education | $69.7M | 7 |
| PRESBYTERIAN COLLEGE | Clinton | L20Z Housing & Shelter | $67.3M | 15 |
| PALMETTO GOODWILL | North Charleston | P20 Human Services | $65.1M | 9 |
| GENESIS HEALTHCARE INC | Columbia | E30 Health Care | $65M | 17 |
| SOUTH CAROLINA STUDENT LOAN CORP | Columbia | W600 Public & Societal Benefit | $65M | 21 |
| LYNCHES RIVER ELECTRIC | Pageland | — | $64.3M | 16 |
| UNIVERSITY OF SOUTH CAROLINA EDUCATIONAL | Columbia | B110 Education | $64.1M | 10 |
| BISHOP GADSDEN EPISCOPAL RETIREMENT | Charleston | P750 Human Services | $63.2M | 13 |
| NATIONAL WILD TURKEY FEDERATION INC | Edgefield | C300 Environment | $63.1M | 10 |
| Newberry College | Newberry | B420 Education | $61.3M | 8 |
| Columbia International University | Columbia | B500 Education | $60.5M | 8 |
| GOODWILL INDUSTRIES OF UPSTATEMIDLANDS | Greenville | J32Z Employment | $58.6M | 9 |
| SOUTH CAROLINA CONNECTIONS | Columbia | B99 Education | $58.3M | 0 |
| BlueCross BlueShield of South Carolina | Columbia | T70 Philanthropy, Voluntarism & Grantmaking Foundations | $57.9M | 0 |
| SOUTH CAROLINA FIRST STEPS TO | Columbia | B012 Education | $57.1M | 4 |
| Health Sciences South Carolina | Columbia | E12 Health Care | $56.6M | 6 |
| EDISTO ELECTRIC COOPERATIVE INC | Bamberg | W80 Public & Societal Benefit | $56.5M | 16 |
| BROAD RIVER ELECTRIC COOPERATIVE | Cowpens | — | $56.2M | 15 |
| TRI-COUNTY ELECTRIC | St Matthews | — | $53.1M | 15 |
| PEACE CENTER FOUNDATION | Greenville | A610 Arts, Culture & Humanities | $50.5M | 6 |
| Spartanburg County Foundation | Spartanburg | T310 Philanthropy, Voluntarism & Grantmaking Foundations | $48.6M | 4 |
| NEWBERRY ELECTRIC COOPERATIVE INC | Newberry | — | $48.6M | 16 |
| Erskine College and Theological Seminary | Due West | B420 Education | $46.6M | 5 |
| LITTLE RIVER MEDICAL CENTER INC | Little River | E22Z Health Care | $46.5M | 11 |
| COASTAL COMMUNITY FOUNDATION OF SOUTH | N Charleston | T310 Philanthropy, Voluntarism & Grantmaking Foundations | $46.3M | 8 |
| SOUTH CAROLINA EPISCOPAL HOME at Still Hopes | W Columbia | E91Z Health Care | $45.8M | 10 |
| MUSC AFFILIATE PHYSICIANS | Charleston | F11 Mental Health & Crisis Intervention | $45.7M | 3 |
| LIMESTONE UNIVERSITY | Gaffney | B42Z Education | $45.7M | 7 |
| HARVEST HOPE FOOD BANK | Columbia | K31Z Food, Agriculture & Nutrition | $45M | 1 |
| CHARLESTON EDUCATIONAL EXCELLENCE | Charleston | N40 Recreation & Sports | $45M | 1 |
| The Inspirational Network Inc | Indian Land | X82 Religion-Related | $43.3M | 25 |
| MEETING STREET SCHOOLS | Charleston | B82 Education | $41.2M | 9 |
| WATER MISSIONS INTERNATIONAL | North Charleston | Q30 International, Foreign Affairs & National Security | $41.1M | 8 |
| NATIONAL COUNCIL OF EXAMINERS | Greenville | U42D Science & Technology | $40.8M | 9 |
| BABCOCK CENTER INC | West Columbia | P820 Human Services | $40.7M | 3 |
