Background Intensive care unit-acquired weakness is a frequent complication of critical illness because of patients' immobility and prolonged use of mechanical ventilation. Objectives To describe daily measurements of peripheral muscle strength in patients receiving mechanical ventilation and explore relationships among factors that influence intensive care unit-acquired weakness. Methods Peripheral muscle strength of 120 critically ill patients receiving mechanical ventilation was measured daily by using a standardized handgrip dynamometry protocol. Three grip measurements for each hand were recorded in pounds-force; the mean of these 3 assessments was used in the analysis. Correlates of intensive care unit-acquired weakness (age, sex, illness severity, duration of mechanical ventilation, medications) were analyzed by using mixed models to explore the relationship to grip strength. Results Median baseline grip strength was variable yet diminished (7.7 pounds-force), with either a pattern of diminishing grip strength or maintenance of the baseline low grip strength over time. With controls for days of measurement, female sex (β = -10.4; P < .001), age (β = -0.24; P = .004), and days receiving mechanical ventilation (β = -0.34; P = .005) explained a significant amount of variance in grip strength over time. Conclusions Patients receiving prolonged mechanical ventilation had marked decrements in grip strength, measured by hand dynamometry, a marker for peripheral muscle strength. Hand dynamometry is a reliable method for measuring muscle strength in cooperative critically ill patients and can be used to develop interventions to prevent intensive care unit-acquired weakness.