Thackery enlists Edwards to help him test a new hypothesis. After rejecting Robertson’s advances at The Knick, Lucy learns that confession isn’t always good for the soul. Young journalist Genevieve Everidge works on a story about one of Thackery’s rivals. Cornelia is dismayed by the limits of her husband’s sympathies. Barrow faces a new adversary at Tammany Hall. Gallinger is intrigued by a discussion of eugenics at a class reunion. Edwards deals with a surprise visitor.

Abby’s worsening condition persuades Thackery to test out his novel syphilis treatment. Edwards comes clean to Opal, but does not get the response he expects. Cleary makes a last-ditch effort to raise funds for Harriet as her date in court arrives. Bertie undergoes physical training. Barrow loses a sponsor. Gallinger’s prejudices are reinforced. Cornelia probes a suspicious death. Lucy laments her lot in life.

Faced with a quandary, Bertie decides to take matters into his own hands at Mt. Sinai, enlisting Algernon to help. Thackery investigates the efficacy of hypnosis, and takes an interest in a pair of conjoined twins. Lucy lobbies Henry for a gala invitation. Cornelia visits the brother of a deceased immigrant with ties to Speight. Gallinger dines with an unwelcome guest. Barrow previews a new home for Junia. Harriet agrees to make a change.

Fighting his nerves, Thackery readies himself to attempt to separate Zoya and Nika in front of a packed audience. After getting a surprise gift from her father-in-law, Cornelia attends a gala charity ball for the new Knick with other familiar guests. Barrow gets rid of a threat. Opal spoils the Robertsons’ good mood. Algernon gets a long-overdue spotlight in the surgical theater, but complications ensue.

Thackery attempts a new cure in the inebriation ward; Brockhurst demands his "girls" be returned; Gallinger and his wife's relationship and Bertie's relationship with Genevieve go off in surprising directions. Later, Cornelia shows evidence of the company's wrongdoing to Henry; Barrow's marriage troubles come to a head; and Thackery performs plastic surgery on Abby.

Thackery and Capt. Robertson's connection and how the doctor arrived at the Knick, are revealed; the problems between Edwards and Gallinger come to a head after a medical-board hearing about Gallinger's vasectomies. Later, Cleary and Harriet engage in a joint business venture; Lucy shares memories with her father; Barrow realizes the rising costs of living well; and Cornelia and Henry face a family crisis.

Thackery ignores Zinberg's advice at Mt. Sinai and undertakes a risky, alternative course of action; Cornelia confronts Henry about the family business; Barrow's actions at the hospital construction site are called into question; Gallinger ponders a job opportunity; and Cleary steadfastly refuses to give up on Harriet.