The prevalence of smallpox during the early years of the American War for Independence posed a very real danger to the success of the Revolution. This essay documents the impact of the deadly disease on the course of military activities during the war and analyzes smallpox as a critical factor in the military decision-making process. Historians have rarely delved into the significant implications smallpox held for eighteenth-century military strategy and battlefield effectiveness, yet the disease nearly crippled American efforts in the campaigns of 1775 and 1776. Smallpox was a major factor during the American invasion of Canada and the siege of Boston. Rumors over the British use of biological warfare, controversy over inoculation, and attempts to control the spread of smallpox all impeded the progress of the war. Recruitment was adversely affected, desertions increased, and commanding officers were forced to proceed with inadequate forces because of smallpox. This frightening disease affected the actions of the Revolutionary army and its generals, reduced the American ability to attract and hold recruits, and influenced the controversial development of preventive medical policies.