Previous studies have reported differential responses to therapeutic interventions depending on the patient's history with bipolar disorder, which highlights the importance of understanding the longitudinal nature of the disorder. The goal of the present analyses was to describe and compare the baseline characteristics, response to treatment, and medication patterns in adult patients experiencing a first episode versus multiple episodes of mania.The European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM) study was a 2-year prospective, observational study to evaluate outcomes in patients experiencing a DSM-IV- or ICD-10-diagnosed manic or mixed episode. The study was conducted from December 2002 to June 2004.Among 3,115 patients, 256 (8.2%) enrolled with a first manic or mixed episode. Relative to multiple-episode patients, first-episode patients were younger and had a lower body mass index (BMI), a higher incidence of past or current cannabis abuse, significantly higher baseline Young Mania Rating Scale total and Clinical Global Impressions-Bipolar Disorder (CGI-BP) mania scores, and lower CGI-BP depression and Hamilton Depression Rating Scale (5-item version) total scores. At the 12-week endpoint, rates of recovery and remission were greater for first-episode patients, and times to recovery and remission were shorter.Limitations of the study were that entry of patients into this study with an acute manic or mixed episode was determined by clinical interview but not confirmed with a structured diagnostic interview. That information on the course of illness prior to entry into the study was obtained retrospectively. First-episode patients presented with different baseline illness characteristics and achieved recovery and remission more rapidly than multiple-episode patients.