The aim of the present study was to investigate clinical and economic consequences of medication non-adherence during 21-month follow-up in the treatment of bipolar disorder following a manic or mixed episode. Data were taken from the European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM), which was a prospective, observational study on patient outcomes with a manic/mixed episode in Europe. Physician-rated adherence was dichotomized as adherence/non-adherence at each assessment. Cox proportional hazards models were employed to investigate the impact of non-adherence on remission, recovery, relapse, recurrence, hospitalization and suicide attempts. Costs of medication and resource use in adherent and non-adherent patients during follow-up were estimated with multivariate analyses. Of the 1341 patients analysed, 23.6% were rated non-adherent over 21 months. Non-adherence was significantly associated with decreased likelihood of achieving remission and recovery as well as increased risk of relapse and recurrence as well as hospitalization and suicide attempts. In addition, costs incurred by non-adherent patients during this period were significantly higher than those of adherent patients (£10231 vs £7379, p less than 0.05). This disparity mainly resulted from differences in inpatient costs (£4796 vs £2150, p less than 0.05). In conclusion, non-adherence in bipolar patients was associated with poorer long term clinical outcomes that have economic implications for health-care providers.