Heart transplantation (HTX) remains the ultimate and gold-standard treatment option for patients with advanced heart failure. Serum lactate level measurements have been proven useful for determining the outcome following other cardiac surgeries and among critically ill patients. The aim of the study was to perform a comprehensive analysis of serum lactate levels in the early postoperative period after HTX. Forty-six patients who underwent HTX between 2010 and 2015 were enrolled in this retrospective study, and detailed hemodynamic and metabolic data from the first 48 postoperative hours were collected and analyzed. Throughout the observation, all of the patients experienced at least one episode of hyperlactatemia, with the median Peak Value of 7.0 (4.5–8.4) mmol/L. Serum lactate level measurement upon ICU admission can be used as a predictive parameter for in-hospital mortality among heart transplant recipients. Values greater than 7.0 mmol/L can predict in-hospital mortality with 90% accuracy. Hemodynamic instability is a more common phenomenon than primary graft dysfunction. Only early postoperative serum lactate levels correspond with hemodynamic instability following HTX. Postoperative hemodynamic instability is associated with poor long-term survival among HTX recipients.