Purpose: We systematically analyzed the lateralizing value of clinical seizure semiology in patients with frontal lobe epilepsy (FLE). Methods: We studied the incidence, positive predictive value (PPV), and the lateralizing significance of various clinical symptoms in 228 seizures (s) of 31 patients (p) with medically refractory FLE (17 with left‐sided and 14 with right‐sided seizure onset). Seizures recorded during prolonged video‐EEG monitoring were assessed by two independent reviewers blinded for the patient's clinical data. Analysis was performed both for patients and seizures. Results: Version 16 p (52%); PPV, 94%; p = 0.001; 47 s (21%); PPV, 75%; p = 0.001, unilateral clonic movements 16 p (52%); PPV, 81%; p = 0.021; 32 s (14%); PPV, 81%; p = 0.001, unilateral dystonic posturing eight p (26%); PPV, 75%; p = 0.289; 46 s (20%); PPV, 80%; p = 0.001, unilateral tonic posturing 10 p (32%); PPV, 80%; p = 0.109; 19 s (7.4%); PPV, 79%; p = 0.019, and unilateral grimacing 10 p (32%); PPV, 100%; p = 0.002; 19 s (8%); PPV, 100%; p = 0.001 were of lateralizing significance, indicating a contralateral seizure onset. Asymmetric ending five p (16%); PPV, 80%; p = 0.375; nine s (4%); PPV, 89%; p = 0.039 after secondarily generalized tonic–clonic seizures was significantly associated with an ipsilateral seizure onset. Pure ictal vocalizations occurred significantly more frequently in seizures of right hemispheric onset 13 p (42%); PPV, 62%; p = 0.581; 63 s (28%); PPV, 73%; p = 0. 001, whereas in individual patients, this symptom showed no lateralizing significance. The remaining clinical symptoms (figure 4 sign, unilateral hand automatisms, early head turning, postictal nose wiping, and unilateral eye blinking) were not of lateralizing significance in our patients. The results of clinical seizure lateralization corresponded with the final lateralization of the seizure‐onset zone in 81% of our patients. Conclusions: Clinical seizure semiology can provide correct information on the lateralization of the seizure‐onset zone in >80% of patients with medically refractory frontal lobe epilepsy.