OBJECTIVES: To perform a systematic review of literature on real-world data from observational studies on bipolar disorder (BD) treatment regarding patterns-of-care, adherence, and clinical outcomes of second-generation atypical antipsychotics (SGA). METHODS: A literature search was performed on Medline and Embase to identify articles on BD addressing patterns-of-care, adherence and clinical outcomes of SGA therapy from 2006 to 2016. RESULTS: Fifty-three studies were included for analysis. Regarding patterns of drug utilization, SGA monotherapy are prescribed for about 45% of patients as first antimanic therapy (quetiapine in 39.5% and aripiprazole in 37.2% of cases). Overall, prescriptions for BD patients include mainly SGA monotherapy or in combination (45-50%) and mood stabilizers (e.g.: lithium, anticonvulsants) for 65-80% of cases. During follow-up, combination therapy (SGA+mood stabilizers) is prescribed to 50-70% of patients. Adherence to clinical guidelines prescription recommendations range from 50%-83%. Adherence to medication was measured by medication possession ratio (MPR), with an MPR³80% considered as appropriate adherence to therapy. Some studies reported very poor adherence rates (MPR: 15-25% and MPR ≥80% for only 6-10% of patients receiving SGA), but the majority reported MPRs ranging from 40-75%. Mean duration of SGA use was 175 to 290 days over a 12-month period, but persistence was described as around 100 days. Reasons for non-adherence were: younger age; baseline substance use disorder; higher disease burden, with a greater number symptoms; side effects as a cause for frustration; comorbid anxiety and obsessive-compulsive disorder. CONCLUSIONS: Observations from real-world evidence are essential components in economic models development and decision-making process. This review showed which patterns-of-care are adopted in real practice for the treatment of BD patients. SGA monotherapy is used for 45% of patients during first antimanic episode, almost 50% of cases receive SGA (monotherapy or combination) overall and up to 70% are treated with SGA plus mood stabilizers during follow-up.