In a retrospective evaluation of 32 inpatients with therapy-resistant epilepsy and intellectual disability, the efficacy of pregabalin (PGB) treatment was assessed after 6 and 12 months. The combined efficacy measure included the percentage reduction in seizure frequency, as well as the Clinical Global Impression (CGI) scale. Tolerability was assessed using a list of the 10 adverse effects most frequently observed in the regulatory studies and also by the CGI scale. After 6 months, the retention rate was 75%. Six patients (18.75%) were responders (50% seizure reduction and/or "good" or "very good" effect on CGI). No patient was seizure free. Seven patients had adverse effects that were not impairing. Eight patients had side effects that were essentially impairing. Weight gain, somnolence, asthenia, and ataxia were the most frequent adverse effects. Rare adverse events were severe mental slowing and loss of daily life capacities on a low dose of PGB in one patient and increase in auto-aggression in another patient. After 12 months, the retention rate was 40.6%, the responder rate was 25%, and one patient was seizure free. Statistical analysis did not identify any predictor of outcome (seizure type, epilepsy syndrome, co-medication, degree of intellectual disability). In this highly selected population, the efficacy of PGB was only moderate.