Objective: The aims of this multi-centre cross-over study were to evaluate the efficacy of valproate in patients with partial epilepsy and compliance with the controlled-release formulation (valproate-CR). Patients and Methods: Ninety-four patients were included in ten centres and 81.9% completed the study. Clinical and demographic features were assessed at baseline, treatment compliance and satisfaction, efficacy and adverse events were evaluated at four visits. Seizure frequency, incidence of adverse events, treatment compliance and patient satisfaction differed significantly between the two treatment periods, with significant improvements in all measures following the switch to valproate-CR. Results: At first visit, 30.5% of patients were either seizure free or experienced rare seizures and were 62.5% at the fifth visit (p<0.001). Adverse events were observed in 35 (37.6%) at the second visit, while this number was 19 patients (25%) at the fifth visit. Treatment compliance was 82.2% at the second visit and this ratio increased to 97.4% at the fifth visit after the transition to long acting valproate form (p=0.001). At study-end, 84.9% of patients were satisfied with the treatment and 74.4% of patients were highly improved. Conclusion: In conclusion, use of valproate-CR was associated with a lower incidence of side-effects and improved patient compliance and satisfaction.