<jats:sec> <jats:title>Background</jats:title> <jats:p>This pilot trial focused on feasibility and safety to provide preliminary data to evaluate the hemostatic potential of cold-stored platelets (2° to 6°C) compared with standard room temperature–stored platelets (20° to 24°C) in adult patients undergoing complex cardiothoracic surgery. This study aimed to assess feasibility and to provide information for future pivotal trials.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>A single center two-stage exploratory pilot study was performed on adult patients undergoing elective or semiurgent complex cardiothoracic surgery. In stage I, a two-armed randomized trial, platelets stored up to 7 days in the cold were compared with those stored at room temperature. In the subsequent single-arm stage II, cold storage time was extended to 8 to 14 days. The primary outcome was clinical effect measured by chest drain output. Secondary outcomes were platelet function measured by multiple electrode impedance aggregometry, total blood usage, immediate and long-term (28 days) adverse events, length of stay in intensive care, and mortality.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>In stage I, the median chest drain output was 720 ml (quartiles 485 to 1,170, n = 25) in patients transfused with room temperature–stored platelets and 645 ml (quartiles 460 to 800, n = 25) in patients transfused with cold-stored platelets. No significant difference was observed. The difference in medians between the room temperature– and cold-stored up to 7 days arm was 75 ml (95% CI, −220, 425). In stage II, the median chest drain output was 690 ml (500 to 1,880, n = 15). The difference in medians between the room temperature arm and the nonconcurrent cold-stored 8 to 14 days arm was 30 ml (95% CI, −1,040, 355). Platelet aggregation in vitro increased after transfusion in both the room temperature– and cold-stored platelet study arms. Total blood usage, number of adverse events, length of stay in intensive care, and mortality were comparable among patients receiving cold-stored and room temperature–stored platelets.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>This pilot trial supports the feasibility of platelets stored cold for up to 14 days and provides critical guidance for future pivotal trials in high-risk cardiothoracic bleeding patients.</jats:p> </jats:sec> <jats:sec> <jats:title>Editor’s Perspective</jats:title> <jats:sec> <jats:title>What We Already Know about This Topic</jats:title> </jats:sec> <jats:sec> <jats:title>What This Article Tells Us That Is New</jats:title> </jats:sec> </jats:sec>