© 2014 American Chemical Society. A novel in vivo flow evaporimeter is developed to measure human tear-evaporation rates. The flow evaporimeter relies on a well-defined flow field to the eye with known and adjustable flow rates and relative humidities, and quantitatively reproduces evaporation rates for pure water. Mass-transfer analysis of the evaporimeter data elucidates, for the first time, the resistance of the human tear-film lipid layer (TFLL) toward minimizing tear loss to the environment. A pilot study on human subjects validates the feasibility of the flow evaporimeter to obtain the tear-film evaporation rates in vivo. Resistance of the TFLL against tear evaporation is found subject specific. Our flow evaporimeter offers an accurate, safe, and convenient diagnostic tool for clinical evaluation of dry-eye-related maladies.