Background: Glycemic control in patients with acute cardiac conditions is a clinical challenge but may substantially improve patient outcome. The aim of the current study was to evaluate the effect of implementing an automated version of an existing insulin protocol for glucose regulation in the Intensive Cardiac Care Unit (ICCU) on compliance with the protocol and achievement of glycemic targets. Methods: During an 11-month period, data of 667 patients with two or more glucose measurements were evaluated, 425 before and 242 after implementation of the clinical decision support system (CDSS) for glucose control at the Erasmus Medical Center ICCU (Rotterdam, The Netherlands). Results: After implementation, compliance with the advised measurement time increased from 40% to 52% (P < 0.001), and compliance regarding insulin dosage increased from 49% to 61% (P < 0.001). Also, more patients had a mean glucose level within the target range of 81-126 mg/dL (31% vs. 43% [P = 0.01]). Monthly evaluation identified reasons for protocol noncompliance (e.g., nutritional status and time of day) and will be used to improve the existing CDSS. Conclusions: The CDSS implementation of an insulin protocol in an ICCU improved compliance, identified targets for further improvement of the protocol, and resulted in improved glucose regulation after implementation.