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Introduction: ICU-acquired weakness (ICU-AW) is a serious complication of critical illness, often linked to mechanical ventilation. Its prevalence and impact among non-intubated ICU patients, however, remain underexplored. We evaluated the burden of ICU-AW and its association with hospital outcomes in this population. Methods: We analyzed adult ICU admissions from the 2022 Nationwide Readmissions Database using ICD-10 codes. ICU-level care was identified using proxy indicators (vasopressors, central lines, CRRT, and IMV). ICU-AW was defined by diagnostic codes for critical illness myopathy or neuropathy. Inverse probability of treatment weighting (IPTW) adjusted for baseline differences. Survey-weighted regression assessed associations with mortality, prolonged stay (>7 days), non-home discharge, LOS, and hospital charges. Results: A total of 1,898,245 adult ICU admissions were identified in NRD-2022. Among these, 30.5% (578,748) patients were intubated, while 69.5%(1,319,497) were managed without intubation. The overall unweighted prevalence of ICU-acquired weakness (ICU-AW) was 9.4 per 1,000 ICU admissions, with a higher prevalence among intubated patients (19.2 per 1,000) compared to non-intubated patients (5.1 per 1,000). The mean age was 59.2 years, and the cohort consisted of 56.6% females. ICU-AW was linked to significantly worse clinical outcomes. After using inverse probability of treatment weighting (IPTW), ICU-AW independently linked to higher odds of in-hospital mortality (aOR, 1.27; p < 0.001), prolonged hospitalization (aOR, 4.17; p < 0.001), and non-home discharge (aOR, 2.65; p < 0.001). Additionally, ICU-AW was associated with more extended hospital stays (β = 8.64 days; 95% CI, 8.42–8.86; p < 0.001), as well as higher total hospital charges (+$105,119; p < 0.001). Conclusions: Our study showed that ICU-acquired weakness is a clinically significant and underrecognized complication in non-intubated critically ill patients. It was independently associated with worse outcomes, including higher mortality, longer hospital stays, and increased healthcare costs. These findings highlight the need for early screening and preventive strategies even among non-intubated patients traditionally considered lower risk