Background and purpose Focal epilepsy of unknown cause (FEUC) is an under-investigated topic despite its remarkable frequency. We aimed to report the long-term follow-up findings along with the drug-response, 5 year remission rates and diagnostic changes to give an insight about the heterogeneous characteristics of FEUC. Methods Demographic, clinical, neurophysiological and imaging data of 196 patients diagnosed as FEUC according to ILAE criteria, with a minimum 5-year follow-up were evaluated in a tertiary epilepsy center. The drug resistance, 5 years of remission and relapse rates were investigated and the subgroups were compared statistically. Results The rate of drug resistance was 21.8% and status epilepticus (p < 0.001), abnormal neurological examination (p = 0.020), seizure onset before 10 years (p = 0.004) and a high initial seizure frequency (p = 0.006) were significant predictors of drug resistance. The rates of terminal 5-year remission, 5-year remission ever and relapse were 39.9%, 44.26% and 24.04%, respectively. There were 13 patients (6.6%) with a changed final diagnosis. Drug resistance (p = 0.004), pathological EEG (p = 0.034) and status epilepticus (p = 0.021) were negative variables for achieving remission. The lobar localization of seizures was not a predictor of remission or relapse. Onset after 10 years of age had a higher probability of achieving a 5-year remission according to Kaplan-Meier curves (p < 0.001). Conclusions Focal epilepsy of unknown cause has a benign electroclinical subgroup with favorable long-term course, lower drug resistance and higher 5 years of terminal remission and remission ever rates, when appropriately treated. Our findings might be valuable in terms of counseling and management of patients with FEUC at the first referral to epilepsy clinics.