Objectives: To longitudinally evaluate the association of post-ICU muscle weakness and associated trajectories of weakness over time with 5-year survival. Design: Longitudinal prospective cohort study over 5 years of follow-up. Setting: Thirteen ICUs in four hospitals in Baltimore, MD. Patients: One hundred fifty-six acute respiratory distress syndrome survivors. Interventions: None. Measurements and Main Results: Strength was evaluated with standardized manual muscle testing using the Medical Research Council sum score (range, 0-60; higher is better), with post-ICU weakness defined as sum score less than 48. Muscle strength was assessed at hospital discharge and at 3, 6, 12, 24, 36, and 48 months after acute respiratory distress syndrome. At discharge, 38% of patients had muscle weakness. Every one point increase in sum score at discharge was associated with improved survival (hazard ratio [95% CI], 0.96 [0.94-0.98]), with similar findings longitudinally (0.95 [0.93-0.98]). Having weakness at discharge was associated with worse 5-year survival (1.75 [1.01-3.03]), but the association was attenuated (1.54 [0.82-2.89]) when evaluated longitudinally over follow-up. Persisting and resolving trajectories of muscle weakness, occurring in 50% of patients during follow-up, were associated with worse survival (3.01 [1.12-8.04]; and 3.14 [1.40-7.03], respectively) compared to a trajectory of maintaining no muscle weakness. Conclusions: At hospital discharge, greater than one third of acute respiratory distress syndrome survivors had muscle weakness. Greater strength at discharge and throughout follow-up was associated with improved 5-year survival. In patients with post ICU weakness, both persisting and resolving trajectories were commonly experienced and associated with worse survival during follow-up.