Thackery weighs performing surgery on a former flame, and orders Gallinger and Chickering to experiment on pigs. Barrow goes the extra yard to square a debt. After a bad day at work, Edwards takes out his frustrations at a local bar. Robertson is relieved when her pleas about treating a patient with typhoid fever are finally heard.

During surgery, Thackery's hand is forced by Algernon, which irks Gallinger. A recovering Abigail regrets her involvement with Thackery and Sister Harriet and Cleary make a couple of deals. Meanwhile, Bertie receives a scolding from his physician father who is unhappy with his son's career path and Lucy becomes privy to Thackery's secrets.

Barrow can alleviate a debt if he treats one of Collier's wounded men and also urges Capt. Robertson to buy one of Thomas Edison's new inventions. Meanwhile, Algernon tries a new approach to hernia surgery, the health of Everett and Eleanor's baby worsens, and Sister Harriet and Cleary head to Chinatown.

After testing out a new procedure, Thackery and Bertie vow to reverse a series of failures in the operating theatre. Euphoric after helping Speight, Cornelia finds herself less than enthusiastic about her status as the future Mrs. Phillip Showalter. Thackery entertains a salesman’s pitch; Everett considers how to help Eleanor with her grief; Barrow haggles over used merchandise. Edwards finds his clinic, and his career, in jeopardy after a surprise encounter.

Already on edge due to a city-wide run on cocaine, Thackery worries that Dr. Levi Zinberg, a Jewish surgeon and inventor, will steal his spotlight at the next New York Surgical Society presentation. Bertie continues his courtship of Lucy while staving off his father’s persistent demands that he leave the Knick. Cornelia, Speight and Bertie go to court in an attempt to keep “Typhoid Mary” Mallon quarantined. Gallinger tries to get Eleanor to move past her grief.

A late-night crime sheds unfavorable light on the Knick, forcing Robertson to come up with hush money. Lucy goes to extremes to get drugs for an increasingly desperate Thackery, whose plea for an advance from a seller of patent medicines falls on deaf ears. Gallinger despairs as Eleanor’s behavior becomes more erratic; Cornelia and Edwards proffer different solutions to a shared dilemma.

Refusing to collaborate with Dr. Zinberg on blood-transfusion research, an increasingly paranoid Thackery pushes himself to the limit, and beyond, in an effort to “solve the riddle” and beat his rival. Cornelia and Edwards arrive at a crossroads; Barrow trades one creditor for another; Lucy requests Bertie’s help. With the Knick in the midst of yet another crisis, Robertson calls for a vote.