| 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. |
| Cara Seymour | Sister Harriet |
| Eric Johnson | Dr. Everett Gallinger |
| David Fierro | Inspector Jacob Speight |
| Maya Kazan | Eleanor Gallinger |
| Leon Addison Brown | Jesse Edwards |
| Grainger Hines | Captain August Robertson |
| Matt Frewer | Dr. J.M. Christiansen |
| Michael Berresse | Parke-Davis Representative |
| William Hill | Archbishop |
| Melissa McMeekin | Mary Mallon |
| Michael Nathanson | Dr. Levi Zinberg |
| Reg Rogers | Dr. Bertram Chickering, Sr. |
| Robert Vincent Smith | Judge |
| Frank Wood | Mr. Havershorn |
| Ken Marks | Mr. Bakerman |
| Annie McNamara | Well Dressed Woman |
| Michael Milligan | President, Metropolitan Surgical Society |
| Richard James Porter | Monsignor Joseph Mills Lawlor |
| Ying Ying Li | Lin-Lin |
| George Morris Fasbinder | (as George Fasbinder) |
| Rusty Hendrickson | Carriage Driver |
| Antwayn Hopper | Woodson |
| Brent Langdon | |
| Leopold Manswell | Hiram |
| Geoff Schuppert | Bailiff |
| Ben Van Bergen | Mr. Tuttle |
| Perry Yung | Ping Wu |
| Jerry DiLeo | Bar Patron |
| Claire Corddry | Pedestrian |
| Sean Harris | Footman |
| David Itchkawitz | Doctor |
| Robert Sage | Surgeon |
| Joseph Anthony Sudol | Surgeon |
| Dominic Wergeland | First Class Passenger |