OBJECTIVE Intensive and quantitative evaluation of the duration, intensity and frequency of tonic and clonic signs of secondarily generalized tonic-clonic seizures (GTCS) in patients with pharmacoresistant partial seizures during topiramate (TPM) treatment. METHODS Thirty patients suffering from refractory partial seizures with secondarily GTCS undergoing presurgical evaluation were randomized into a low dosage (100 mg daily) and a parallel medium dosage (200 mg daily) group of TPM add-on medication (15 patients for each group). Study phases included a 3 days baseline video-EEG phase, a 10 days TPM titration phase without video-EEG and a 3 days TPM dose maintenance phase with video-EEG. During the baseline and the dose maintenance phase seizures were recorded using video-EEG monitoring and the following parameters were measured for each recorded secondarily generalized tonic and clonic signs: duration (lasting seconds), intensity (on a 0-3 scale), frequency (numbers per 24 h). RESULTS A total of 46 complex partial seizures with secondarily generalized tonic-clonic signs during the baseline phase and 20 during the dose maintenance phase were intensively analyzed. More patients in the medium dosage group than in the low dosage groups were free from secondarily GTCS during the dose maintenance phase (nine vs. two, P<0.05). Intergroup comparison suggested that the duration of all tonic signs decreased more in the medium dosage group computing the reduction from baseline to the dose maintenance phase (P<0.05). There were statistically more significant reductions in the duration and intensity of clonic signs in the medium dosage group (P<0.05). CONCLUSIONS TPM has an early dose-dependant effect on secondarily GTCS in patients with pharmacoresistant partial seizures. The present study intensively analyzed the duration, intensity, and frequency of secondarily generalized tonic and clonic signs in patients with pharmacoresistant partial seizures. The quantitative data suggested that TPM had a robust early inhibitory effect on secondarily generalized tonic-clonic signs; effects were more prominent in the medium dosage group (200 mg daily) than in the low dosage group (100 mg daily).