Background: Bipolar disorder (BD) is a severe chronic psychiatric disorder affecting 0.5 to 1% of the population worldwide. To date, most studies have estimated the cost of BD via information sourced from insurance claims with limited information on clinical characteristics and course of BD. The aims of this study are (i) to estimate the direct healthcare cost associated with BD and to identify contributing factors and (ii) to study the evolution of cost during a two-year follow-up period. Method: We analyzed a sample of 1116 individuals with BD included in the Advanced Centers of Expertise in Bipolar Disorder cohort. We estimated the direct healthcare cost per year and per patient, and we identified the clinical features of patients with BD associated with higher direct healthcare costs. In a subsample of patients followed up for two years centers of expertise for BD, we studied the evolution of direct healthcare cost. Results: The average cost of bipolar disorder was € 6910 per year and per patient. Clinical features of BD, sociodemographic characteristics, and associated addiction were associated with higher direct healthcare costs. In the subsample of patients followed-up for two years, direct healthcare cost dropped by more than 50%, strongly suggesting the beneficial effect of specialized care organization. Limitation: We did not estimate indirect healthcare and intangible costs. Conclusion: Our study investigates the cost of BD and its evolution in a deeply phenotyped longitudinal sample. Cost-utility and cost-effectiveness analyses are required to inform resource allocation decisions and to promote innovative healthcare organizations. © 2022< Réduire