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Hyponatremia is a risk factor for adverse surgical outcomes, but limited information is available on the prognosis of hyponatremic patients who undergo total knee arthroplasty (TKA). The purpose of this investigation was to compare the incidence of major morbidity (MM), 30-day readmission, 30-day reoperation, and length of hospital stay (LOS) between normonatremic and hypontremic TKA patients.The American College of Surgeons National Surgical Quality Improvement Program database was used to identify all primary TKA procedures. Hyponatremia was defined as <135 mEq/L and normonatremia as 135 to 145 mEq/L; hypernatremic patients (>145 mEq/L) were excluded. Multivariable logistic regression was used to determine the association between hyponatremia and outcomes after adjusting for demographics and comorbidities. An α level of 0.002 was used and calculated using the Bonferroni correction. Our final analysis included 88,103 patients of which 3,763 were hyponatremic and 84,340 were normonatremic preoperatively. In our multivariable models, hyponatremic patients did not have significantly higher odds of experiencing an MM (odds ratio [OR]: 1.05; 99% confidence interval [CI] 0.93-1.19) or readmission (OR: 1.12; 99% CI: 1-1.24). However, patients with hyponatremia did experience significantly greater odds for reoperation (OR: 1.24; 99% CI: 1.05-1.46) and longer hospital stay (OR: 1.15; 99% CI: 1.09-1.21). We found that hyponatremic patients undergoing TKA had increased odds of reoperation and prolonged hospital stay. Preoperative hyponatremia may be a modifiable risk factor for adverse outcomes in patients undergoing TKA, and additional prospective studies are warranted to determine whether preoperative correction of hyponatremia can prevent complications., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)