OBJECTIVE Adverse effects of anti epileptic drugs (AEDs) can significantly affect the life of people with epilepsy. We used a register to determine if polytherapy with AED has more adverse effects than monotherapy. METHODS We established a register for people with epilepsy (www.UKAED.info). Participants were requested to complete the Liverpool Adverse Event Profile (LAEP) to quantify adverse effects. We also recorded type of epilepsy, seizure control and AED including drug doses. Five hundred and seventy six complete data sets were available, monotherapy (n=186), polytherapy (n=325) and control subjects not taking AED (n=65). RESULTS The mean LAEP scores in polytherapy (45.56, confidence interval (CI)=44.36-46.76) were significantly higher than the mean LAEP scores in monotherapy (42.29, CI=40.65-44.02) and the mean LAEP scores in controls (33.25, CI=31.05-35.44). Tiredness, memory problems and difficulty concentrating were the most common symptoms in patients taking AED and were consistently higher in polytherapy than in monotherapy. Tiredness was reported as always or sometimes being a problem in (polytherapy/monotherapy/controls) 82.5%/75.6%/64.6%, memory problems in 76%/63.2%/29.2% and difficulty concentrating in 68%/63.9%/30.8%. The proportion of seizure-free patients was significantly lower in the polytherapy group (17%) than in the monotherapy group (55%). Depression rates between the monotherapy and polytherapy groups were similar. Drug dosages were higher in polytherapy, however this did not reach statistical significance. CONCLUSIONS Patients on polytherapy had significantly higher LAEP scores than patients on monotherapy. This should be carefully discussed with the patient before a second AED is added.