Background Recent studies have demonstrated safety, feasibility, and decreased hospital length of stay for patients with weakness acquired in the intensive care unit (ICU) who receive early physical rehabilitation. The scored Physical Function in Intensive Care Test (PFIT-s) was specifically designed for this population and demonstrated excellent psychometrics in an Australian ICU population. Objective The purpose of this study was to determine the responsiveness and predictive capabilities of the PFIT-s in patients in the United States admitted to the ICU who required mechanical ventilation (MV) for 4 days or longer. Methods This nested study within a randomized trial administered the PFIT-s, Medical Research Council (MRC) sum score, and grip strength test at ICU recruitment and then weekly until hospital discharge, including at ICU discharge. Spearman rho was used to determine validity. The effect size index was used to calculate measurement responsiveness for the PFIT-s. The receiver operating characteristic curve was used in predicting participants' ability to perform functional components of the PFIT-s. Results From August 2009 to July 2012, 51 patients were recruited from 4 ICUs in the Denver, Colorado, metro area. At ICU discharge, PFIT-s scores were highly correlated to MRC sum scores (rho=.923) and grip strength (rho=.763) (P<.0005). Using baseline test with ICU discharge (26 pairs), test responsiveness was large (1.14). At ICU discharge, an MRC sum score cut-point of 41.5 predicted participants' ability to perform the standing components of the PFIT-s. Limitations The small sample size was a limitation. However, the findings are consistent with those in a larger sample from Australia. Conclusions The PFIT-s is a feasible and valid measure of function for individuals who require MV for 4 days or longer and who are alert, able to follow commands, and have sufficient strength to participate.