In this study we report the results of surgery in a large population of patients affected by drug-resistant focal sleep related epilepsy (SRE) and the identified prognostic factors. We conducted a retrospective analysis of a case series of 955 patients operated on for drug-resistant focal epilepsy from 1997 to 2009. Ninety-five patients with focal SRE and a follow-up of at least 2 years were identified. Presurgical, surgical and histopathological variables were analyzed. Risk of seizures recurrence was assessed by univariate and multivariate analysis. Mean age at epilepsy onset was 5.6 ± 4.9 years. MRI revealed a focal abnormality in 78.9% of cases. Sixty-two percent of patients required a Stereo-EEG investigation. The cortical resection involved the frontal lobe in 61.1% of cases, while in 38.9% an extrafrontal resection was performed. Focal cortical dysplasia (FCD) type II was the most frequent histopathological finding. Mean postoperative follow-up was 82.3 months. Seventy-three patients (76.8%) were in Engel's class I. At univariate analysis, variables associated with a favorable outcome were: absence of Stereo-EEG investigation; positive MRI; complete removal of the Epileptogenic Zone (EZ); presence of FCD type II and FCD type IIb. A diagnosis of FCD type I was associated with postoperative recurrence of seizures. Multivariate analysis identified the complete removal of the EZ and FCD type I as independent predictors of a favorable and unfavorable outcome respectively. SRE can frequently originate outside the frontal lobe and a favorable surgical outcome is achieved in three-fourths of cases independently from the location of the EZ.