Background: The force–frequency relationship is an innate property of the myocardium to alter contractile force due to the changes in calcium cycling related to heart rate. The well-described changes in calcium cycling following cardiopulmonary bypass may, therefore, have important implications for postoperative ventricular performance. Methods: We studied neonates undergoing the arterial switch procedure. Baseline force–frequency relationship was studied using a new tissue Doppler index of contractility, isovolumic acceleration, during transoesophageal atrial pacing prior to sternotomy. Tissue Doppler imaging was performed using a System V ultrasound scanner (GE Vingmed). The left-ventricular free wall was interrogated in an apical 4-chamber view. Postoperative assessments were made during atrial pacing using epicardial pacing wires. Results: We studied 11 neonates undergoing the arterial switch procedure for transposition. Preoperatively maximal isovolumic acceleration was 3.6 m/s², and this occurred at an optimal heart rate of 190 beats/min. Postoperative force–frequency relationships showed a much flatter response with significantly depressed values of isovolumic acceleration (p < 0.001 ANOVA). There was a slight improvement in contractile force at 24 h as compared with 6 h postoperatively, though this was not significantly different. Conclusion: For the first time, these data show non-invasively the disruptive effects of cardiopulmonary bypass on the force–frequency relationship. There is depression of both the maximal contractile force generated and also the slope of the force–frequency relationship. Heart rates greater than the optimal heart rate would be clearly detrimental to ventricular performance. These novel data may allow postoperative manipulation of contractile performance by modulation of heart rate.