A thermoelectric generator (TEG) can be used to harvest electrical energy from human body heat for the purpose of powering wearable electronics. At the NSF Advanced Self-Powered Systems of Integrated Sensors and Technologies (ASSIST), TEGs are one of the enabling technologies being explored to advance the center’s mission of creating wearable, self-powered, health and environmental monitoring systems. As part of this effort, an exploration of the relevant parameters for maximizing the wearable TEG power output from the body heat and maintaining the body comfort is particularly important. For this purpose, the heat from the body must be directed into TEG with minimal loss, the generator must be designed for maintaining a high temperature differential across the thermoelectric material, and the generator must have a small form factor to maintain the body comfort. In order to address these requirements, an optimum TEG design was developed and experiments were conducted both on a temperature-controlled hot plate and on different body locations including the wrist, upper arm, and chest. The TEG was further fabricated into a T-shirt and the power was recorded for different human activities. Comparison of the experiments on various body locations and on the T-shirt yielded the highest to lowest power generated on the upper arm, wrist, chest and T-shirt, respectively. The prospect of powering a wearable electrocardiogram sensor by a TEG on the upper arm is discussed.