BACKGROUND: Little is known about the association between serum potassium level on hospital arrival and neurological outcome after out-of-hospital cardiac arrest (OHCA). We investigated whether the serum potassium level on hospital arrival had prognostic indications for patients with OHCA. METHODS: This prospective, multicenter observational study conducted in Osaka, Japan (CRITICAL study) enrolled consecutive patients with OHCA transported to 14 participating institutions from 2012 to 2016. We included adult patients aged ⩾18 years with OHCA of cardiac origin who achieved return of spontaneous circulation and whose serum potassium level on hospital arrival was available. Based on the serum potassium level, patients were divided into four quartiles: Q1 (K ⩽3.8 mEq/L), Q2 (3.8< K⩽4.5 mEq/L), Q3 (4.5< K⩽5.6 mEq/L) and Q4 (K >5.6 mEq/L). The primary outcome was one-month survival with favorable neurological outcome, defined as cerebral performance category scale 1 or 2. RESULTS: A total of 9822 patients were registered, and 1516 of these were eligible for analyses. The highest proportion of favorable neurological outcome was 44.8% (189/422) in Q1 group, followed by 30.3% (103/340), 11.7% (44/375) and 4.5% (17/379) in the Q2, Q3 and Q4 groups, respectively ( p<0.001). In the multivariable analysis, the proportion of favorable neurological outcome decreased as the serum potassium level increased ( p<0.001). CONCLUSIONS: High serum potassium level was significantly and dose-dependently associated with poor neurological outcome. Serum potassium on hospital arrival would be one of the effective prognostic indications for OHCA achieving return of spontaneous circulation.