Abstract The Interim Resistance Exercise Device (iRED), developed for the International Space Station (ISS), was evaluated using human subjects for a “Man-In-The-Loop Test” (MILT). Thirty-two human subjects exercised using the iRED in a test that was conducted over a 63-working-day period. The subjects performed the same exercises that will be used on board ISS, and the iRED operating constraints that are to be used on ISS were followed. In addition, eight of the subjects were astronauts who volunteered to be in the evaluation in order to become familiar with the iRED and provide a critique of the device. The MILT was scheduled to last for 57,000 exercise repetitions on the iRED. This number of repetitions was agreed to as a number typical of that expected during a 3-person, 17-week ISS Increment. One of the canisters of the iRED failed at the 49,683-repetition mark (87.1% of targeted goal). The remaining canister was operated using the plan for operations if one canister fails during flight (contingency operations). This canister remained functional past the 57,000-repetition mark. This report details the results of the iRED MILT, and lists specific recommendations regarding both operation of the iRED and future resistance exercise device development.