Clinical research on drug intoxication is necessary for appropriate action in emergency departments (EDs). However, currently, there are no evident biomarkers for predicting adverse events (AEs) in patients with drug intoxication. We aimed to evaluate the prognostic value of serum lactate concentrations and lactate kinetics for AEs such as cardiogenic or respiratory failure in patients admitted to the ED with acute drug overdose. We conducted a single-center retrospective study by reviewing the prospective suicide registry of patients visiting the ED. The primary outcome was composite AEs at any point during the ED visit or hospital stay. A total of 566 patients with acute drug overdose were enrolled in this study. Of these, 62 patients had AEs, whereas 363 patients did not, yielding an AE rate of 14.6%. The median 0 h lactate concentrations in the AE and non-AE groups were 2.7 [2.1-5.1] mmol/L and 2.1 [1.4-2.9] mmol/L, respectively (p < 0.001). The median 6 h lactate concentrations in the AE and non-AE groups were 2.0 [1.5-3.9] mmol/L and 1.3 [0.9-2.2] mmol/L, respectively (p < 0.001). The area under the curve of lactate at 0 h for predicting AEs was 0.705 (95% CI: 0.659-0.748). The optimal lactate cutoff point was 4.2 mmol/L (37.1% sensitivity, 92.8% specificity). Multivariable analysis using a stepwise backward method showed that the 0 h lactate concentration was associated with AEs in acute drug intoxication after adjusting for confounders (adjusted OR of 0 h lactate, 1.47; 95% CI, 1.23-1.77). However, the 6 h lactate concentrations, lactate clearance, and delta lactate levels did not predict the outcomes. Lactate concentrations and kinetics in patients admitted to the ED with an acute drug overdose exhibited limited prognostic utility in predicting AEs and should be interpreted with caution when considered for clinical decision-making.