Experimental studies reported that osteopontin (OPN), a matricellular protein, is induced in brain after subarachnoid hemorrhage (SAH). The aim of this study was to investigate the relationships between plasma OPN levels and outcome after aneurysmal SAH in a clinical setting. This is a prospective study consisting of 109 aneurysmal SAH patients who underwent aneurysmal obliteration within 48 h of SAH. Plasma OPN concentrations were serially determined at days 1-3, 4-6, 7-9, and 10-12 after onset. Various clinical factors as well as OPN values were compared between patients with 90-day good and poor outcomes. Plasma OPN levels were significantly higher in SAH patients compared with control patients and peaked at days 4-6. Poor-outcome patients had significantly higher plasma OPN levels through all sampling points. Receiver-operating characteristic curves demonstrated that OPN levels at days 10-12 were the most useful predictor of poor outcome at cutoff values of 915.9 pmol/L (sensitivity, 0.694; specificity, 0.845). Multivariate analyses using the significant variables identified by day 3 showed that plasma OPN ≥ 955.1 pmol/L at days 1-3 (odds ratio, 10.336; 95% confidence interval, 2.563-56.077; p < 0.001) was an independent predictor of poor outcome, in addition to increasing age, preoperative World Federation of Neurological Surgeons grades IV-V, and modified Fisher grade 4. Post hoc analyses revealed no correlation between OPN levels and serum levels of C-reactive protein, a non-specific inflammatory parameter, at days 1-3. Acute-phase plasma OPN could be used as a useful prognostic biomarker in SAH.