Objective To explore the clinical characteristics of patients with combined use of ≥2 kinds of anti-seizure medications in Tibetan plateau. Methods Epilepsy patients who were hospitalized in the People’s Hospital of Tibet Autonomous Region from September 2018 to September 2023 and used ≥2 kinds of anti-seizure medications in combination were selected. Their demographic data such as gender, age, and ethnicity, as well as diagnostic information, medication and other clinical data were collected, and relevant demographic and clinical characteristics were analyzed. In the later stage, telephone follow-up was used to record medication and epileptic seizure control. Results A total of 2295 patients with epilepsy were included, of which 142 (6.2%) met the inclusion criteria, of which 133 (93.7%) were Tibetans. There were more males than females (86 vs. 56, P<0.05), and more minors and young patients than middle-aged and elderly patients (106 vs. 36, P<0.05). 87.3% of the patients underwent magnetic resonance imaging (MRI) or computed tomography (CT), and 71.1% of the patients were abnormal. The main cause of epilepsy was structural etiology (84/142, 59.2%). The most common combination was two drugs (127/142, 89.4%). The largest proportion of combination was sodium valproate and levetiracetam (46/142, 32.4%). After standardized multi-drug combination therapy, the average frequency of epilepsy seizures was significantly reduced compared with the baseline, and the difference was statistically significant (P<0.05). Among the 98 patients aged ≥14 years, 15 cases (15.3%) had drug-refractory epilepsy, 18 cases (18.4%) had seizures controlled by standardized combination medication, 16 cases (16.3%) had seizures controlled by reducing combination medication to a single drug, 5 cases (5.1%) had good control and had stopped medication, 3 cases (3.1%) had frequent epileptic seizures due to poor medication compliance, 15 cases (15.3%) had irregular medication, 17 cases (17.3%) died, and 9 cases (9.2%) were lost. Conclusion The proportion of epilepsy treated with multiple drugs and refractory to drugs was lower than the conclusion of previous studies, and the anti-epileptic effect of multiple drugs was positive. Structural causes (stroke, etc.) are the main causes of epilepsy, and brain parasitic infection is a unique factor of high-altitude epilepsy. Strengthening the standardized use of drugs will help improve the treatment status and prognosis of patients.