Purpose: Seizure and syncope are main causes of patient visits to an emergency department (ED). However, differentiating two diseases through history taking and several ancillary tests is difficult in an ED. Some reports have claimed that ammonia or lactate could differentiate between seizure and other medical diseases. Therefore, this study evaluated the ability of ammonia and lactate to differentiate seizure and syncope. Methods: We reviewed the medical records of 388 patients who visited an ED with seizure or syncope. There were 271 patients in the seizure group (69.8%) and 117 patients in the syncope group (30.2%). Ammonia and lactate levels were compared between the two groups. The optimal level of ammonia and lactate, and their sensitivity and specificity, were evaluated to determine their ability to differentiate seizure and syncope. Results: There were more male in seizure group (66%), but the average age was higher in the syncope group (51± 21 yrs) (p<0.05). The time interval from symptom to ED was similar between the two groups (seizure group: 213± 803 min and syncope group: 184±512 min, p=0.724). The mean ammonia level in the seizure group was higher than the syncope group (85±86 μg/dl and 49±29 μg/dl, respectively, p<0.001). The mean lactate level was also higher in the seizure group than the syncope group (3.5±2.9 mmol/L and 1.6±1.5 mmol/L, respectively, p<0.05). When the cutoff value for ammonia was 50 μg/dL [Area under curve (AUC): 0.617, 95% CI: 0.556-0.678] the sensitivity was 61% and the specificity was 52%. When the cut-off value for lactate was 2 mmol/L [AUC: 0.745, 95% CI: 0.692-0.798] the sensitivity was 60% and the specificity was 76%. Conclusion: Serum ammonia or lactate may serve as an ancillary method for differentiating seizure and syncope, but their sole application is unacceptable due to their low sensitivity and specificity.