BACKGROUND: Osmotic demyelination syndrome (ODS) is a rare but potentially devastating neurologic complication of hyponatremia. The primary objective of this study was to identify the proportion of patients who developed ODS in a large, contemporary, multicenter cohort of patients admitted to the hospital with hyponatremia. METHODS: We conducted a multicenter cohort study of patients admitted with hyponatremia at five academic hospitals in Toronto, Ontario, Canada, between April 1, 2010, and December 31, 2020. All adult patients presenting with hyponatremia (serum sodium level 8 mmol/l in any 24-hour period). RESULTS: Our cohort included 22,858 hospitalizations with hyponatremia. Approximately 50% were women, the average age was 68 years, and mean initial serum sodium was 125 mmol/l (standard deviation, 4.6), including 11.9% with serum sodium from 110 to 119 mmol/l and 1.2% with serum sodium less than 110 mmol/l. Overall, rapid correction of serum sodium occurred in 3632 (17.7%) admissions. Twelve patients developed ODS (0.05%). Seven (58%) patients who developed ODS did not have rapid correction of serum sodium. CONCLUSIONS: In this large multicenter study of patients with hyponatremia, rapid correction of serum sodium was common (n=3632 [17.7%]), but ODS was rare (n=12 [0.05%]). Future studies with a higher number of patients with ODS are needed to better understand potential causal factors for ODS.