Background Non-adherence should always be investigated when there is a failure in bipolar treatments, since it is known that reported non-adherence rates in bipolar disorder treatment for long-term prophylactic pharmacotherapy range from 18% to 52%, with a median prevalence of 44.7%. Several factors are related to the poor adherence and reduction of medication efficiency, such as the different types of bipolar disorder, the presence of side effects, medication interactions, level of patient's knowledge about the disorder and their attitude towards treatment, complexity of medical regimens and the doctor–patient relationship. Methods Bipolar disorder outpatients under lithium treatment from the Hospital de Clínicas and Materno Infantil Presidente Vargas of Porto Alegre were recruited. All the patients had bipolar disorder and gave informed consent to participate in a clinical interview (106), answered the Lithium Attitudes Questionnaire (LAQ), Lithium Knowledge Test (LKT), Medication Adherence Rating Scale (MARS) and had plasma and red blood cells lithium measurements to assess their medication adherence and the factors that influenced it. Results 85.6% of bipolar disorder were adherent to lithium treatment showing plasma lithium between 0.6 and 1.2 mmol/L. There was an inverted correlation between the total LAQ score with plasma and red blood cells, a positive correlation between LKT and MARS with plasma and red blood cell lithium. Conclusion These results confirmed that knowledge level is directly correlated to treatment adherence and patients' attitudes, lower adherence, general opposition to prophylaxis, fear of side effects, denial of therapeutic effectiveness and illness severity.