INTRODUCTION/AIMS: Postoperative myasthenic crisis (POMC), which occurs specifically after thymectomy in myasthenia gravis (MG) patients, is a serious complication with known risk factors such as prior myasthenic crisis. However, the predictive value of perioperative blood lactic acid levels (BLAL) for POMC remains unclear. This study aims to determine whether changes in perioperative BLAL can predict POMC in MG patients undergoing thymectomy. METHODS: A total of 340 patients diagnosed with MG and undergoing thymectomy at the First Affiliated Hospital of Sun Yat-sen University were enrolled (January 2008-September 2018). Multivariate logistic regression analyses were employed to discern independent factors linked with POMC. RESULTS: Among the patients with POMC, notable differences including higher Myasthenia Gravis Foundation of America (MGFA) stage, and history of preoperative myasthenic crisis were observed. Higher postoperative lactic acid levels and the extent of changes were more prevalent in the POMC group. The multivariate analysis unveiled history of myasthenic crisis (odds ratio, OR: 67.18), postoperative BLAL change ratio greater than 50% (OR: 2.86), the video-assisted thoracoscopic surgery (VATS) approach (OR: 4.33), and higher preoperative BLAL (OR per unit: 2.68) were associated with POMC. Both continuous and grouped lactic acid models demonstrated a good predictive capability, yielding area under the curve (AUC) values of 0.84 and 0.83, respectively. The optimal threshold for 24-h postoperative BLAL was 1.98 mmol/L. DISCUSSION: These findings offer valuable insights for clinical decision-making and monitoring of prognosis in managing patients with MG. Future research should explore further the underlying mechanisms linking elevated lactate levels to POMC.