The aim of this study was to assess whether serum albumin concentration upon hospital arrival had prognostic indications on out-of-hospital cardiac arrest (OHCA). This prospective, multicenter observational study conducted in Osaka, Japan (the CRITICAL [Comprehensive Registry of Intensive Cares for OHCA Survival] study), enrolled all patients with consecutive OHCA transported to 14 participating institutions. We included adult patients aged ≥18 years with nontraumatic OHCA who achieved return of spontaneous circulation and whose serum albumin concentration was available from July 2012 to December 2014. Based on the serum albumin concentration upon hospital arrival, patients were divided into quartiles (Q1 to Q4), namely, Q1 (<2.7 g/dl), Q2 (2.7 to 3.1 g/dl), Q3 (3.1 to 3.6 g/dl), and Q4 (≥3.6 g/dl). The primary outcome was 1-month survival with favorable neurological outcome (cerebral performance category scale 1 or 2). During the study period, a total of 1,269 patients with OHCA were eligible for our analyses. The highest proportion of favorable neurological outcome was 33.5% (109 of 325) in the Q4 group, followed by 13.2% (48 of 365), 5.0% (13 of 261), and 3.5% (11 of 318) in the Q3, Q2, and Q1 groups, respectively. In the multivariable logistic regression analysis, the proportion of favorable neurological outcome in the Q4 group was significantly higher, compared with that in the Q1 group (adjusted odds ratio 8.61; 95% confidence interval 4.28 to 17.33). The adjusted proportion of favorable neurological outcome increased in a stepwise manner across increasing quartiles (p for trend <0.001). Higher serum albumin concentration was significantly and independently associated with favorable neurological outcome in a dose-dependent manner.