This commonplace book was filmed exactly as bound and contains notes on medicine, diseases, and weather; poems by Erasmus Darwin and others; family genealogy; letters; and sketches. There are notes by other family members, including his wife, his daughter, and his brother. There is a letter to "Major Darwin" dated 1929 taped inside the front cover, recounting the provenance of the book.

This volume contains medical notes by Wistar, including observations on yellow fever and arguments to prove its foreign origin, facts relative to the progress of the fever in 1797, the infection and death of Colonel Van Emburgh, the infection of the crew of the ship "Deborah" and of the Durham boat (1802), an account of the diseases which afflicted the family of James Hammar in Montgomery County (Pa.), facts relating to the typhus fever of 1812-1813, case histories (1796-1803), temperature chart (1758-1759, 1760), and a thermometrical journal (1760-1765) kept by Charles Norris and copied by Wistar from notes in possession of Joseph Parker Norris.