OBJECTIVE: Several psychiatric medications have the potential to prolong the QTc interval and subsequently increase the risk for ventricular arrhythmias such as torsades de pointes (TdP). There is limited guidance for clinicians to balance the risks and benefits of treatments. METHODS: After a review of the existing literature, clinical-educators from the Association of Medicine and Psychiatry developed expert consensus guidelines for ECG monitoring of the QTc interval for patients with medical and psychiatric comorbidities who are prescribed medications with the potential to prolong the QTc interval. A risk score was developed based on risk factors for QTc prolongation to guide clinical decision-making. RESULTS: A baseline ECG may not be necessary for individuals at low risk for arrythmia. Those individuals with a risk score of two or more should have an ECG prior to the start of a potentially QTc-prolonging medication or be started on a lower risk agent. Antipsychotics are not equivalent in causing QTc prolongation. A consensus-based algorithm is presented for the management of those identified at high (QTc >500 msec), intermediate (males with QTc 450-499 msec or females with QTc > 470-499 msec), or low risk. CONCLUSIONS: The proposed algorithm can help clinicians in determining whether ECG monitoring should be considered for a given patient. These guidelines preserve a role for clinical judgment in selection of treatments that balance the risks and benefits, which may be particularly relevant for complex patients with medical and psychiatric comorbidities. Additional studies are needed to determine whether baseline and serial ECG monitoring reduces mortality.