| Clive Owen | Dr. John W. Thackery |
| André Holland | Dr. Algernon Edwards |
| Jeremy Bobb | Herman Barrow |
| Juliet Rylance | Cornelia Robertson |
| Eve Hewson | Nurse Lucy Elkins |
| Michael Angarano | Dr. Bertie Chickering Jr. |
| Chris Sullivan | Tom Cleary |
| Cara Seymour | Sister Harriet |
| Eric Johnson | Dr. Everett Gallinger |
| Maya Kazan | Eleanor Gallinger |
| Grainger Hines | Captain August Robertson |
| Zaraah Abrahams | Opal Edwards |
| Charles Aitken | Henry Robertson |
| LaTonya Borsay | Evaline Edwards |
| Tom Lipinski | Phillip Showalter |
| Michael Nathanson | Dr. Levi Zinberg |
| Michael Cumpsty | Judge Parkinson Bothamly |
| Linda Emond | Anne Chickering |
| Jennifer Ferrin | Abigail Alford |
| Rachel Annette Helson | Susie |
| Ben Livingston | Dr. William H. Mays |
| Molly Price | Effie Barrow |
| Anthony Rapp | Dr. Thurman Drexler |
| Reg Rogers | Dr. Bertram Chickering, Sr. |
| Erin Wilhelmi | Lottie |
| Happy Anderson | Jimmy |
| Annabelle Attanasio | Dorothy Walcott |
| Lily Brahms | Clara Chickering |
| Blair Busbee | High Society Woman |
| Helen Cespedes | Society Woman #2 |
| Libby Collins | Speight's Neighbor |
| Johanna Day | Eunice Showalter |
| Colman Domingo | Dr. Russell Daniels |
| Wally Dunn | Dr. Grindin |
| Ylfa Edelstein | Nurse Baker |
| Eleni Fuiaxis | Mrs. Gianoulis |
| Jenna Gavigan | High Society Woman |
| Sydney Hollis | Bailiff |
| Brian Kerwin | Corky Vanderbilt |
| Emily Kinney | Nurse Daisy Ryan |
| Joseph McKenna | Man Following Cornelia |
| Aedin Moloney | Sister Mary Michael |
| John O'Creagh | Tammany Hall Official |
| James Joseph O'Neil | Dr. Grindin |
| Ciarán O'Reilly | Priest
(as Ciaran O'Reilly) |
| Zack Phillips | Wendell
(as Zachary Phillips) |
| Alexandra Roxo | Cate |
| Suzanne Savoy | Victoria Robertson |
| Britian Seibert | High Society Woman |
| Gary Simpson | Hobart Showalter |
| Athan Sporek | Paulo (Street Urchin) |
| Forrest Weber | Policeman |
| Frank Wood | Mr. Havershorn |
| Annie Young | Nurse Howland |
| Kelly Aaron | Society Lady
(uncredited) |
| Jonah Coppolelli | Paper Boy, Working Class Boy
(uncredited) |
| Abigail Friend | Patient
(uncredited) |
| James Jackson Jr. | Dancer
(uncredited) |
| Jillian Kinsey | Young Society Woman
(uncredited) |
| Kate MacCluggage | Mary
(uncredited) |
| Aly Mang | Young Society Woman
(uncredited) |
| NaTonia Monét | Floor Dancer
(uncredited) |
| Christian Paul Sherwood | Patient
(uncredited) |
| Jesse VanDerveer | Patient
(uncredited) |