Purpose: Critical illness survivors commonly have impaired physical functioning. Physical therapy interventions delivered in the intensive care unit can reduce these impairments, but the safety of such interventions within routine clinical practice requires greater investigation. Materials and Methods: We conducted a prospective observational study of routine physical therapy from July 2009 through December 2011 in the Johns Hopkins Hospital Medical Intensive Care Unit in Baltimore, MD. The incidence of 12 types of physiological abnormalities and potential safety events associated with physical therapy were monitored and evaluated for any additional treatment, cost, or length of stay. Results: Of 1787 admissions of at least 24 hours, 1110 (62%) participated in 5267 physical therapy sessions conducted by 10 different physical therapists on 4580 patient-days. A total of 34 (0.6%) sessions had a physiological abnormality or potential safety event, with the most common being arrhythmia (10 occurrences, 0.2%) and mean arterial pressure greater than 140 mm Hg (8 occurrences; 0.2%) and less than 55 mm Hg (5 occurrences; 0.1%). Only 4 occurrences (0.1%) required minimal additional treatment or cost, without additional length of stay. Conclusions: In this large, single-center study, routine care physical therapy interventions were safe for critically ill patients.