OBJECTIVES: To perform a systematic literature review (SR) of studies in peer reviewed journals on 10 epidemiologic aspects of BD-I in the US: its annual incidence, prevalence and respective trends; mortality rates and trends; associated comorbid disorders; stages, severity levels and its natural progression. METHODS: A literature search was performed using relevant search terms to identify articles published between 2006 and 2016. Studies were identified through electronic Embase, MEDLINE, and PubMed databases. Manual review of bibliographies allowed for the detection of complementary studies. RESULTS: Eleven SR and five complementary studies addressed the incidence and prevalence of BD-I. US National Institute of Mental Health (NIMH) estimated the prevalence of BD-I as 1% (lifetime) and 0.6% (12-month). Mean age of disease onset was 20 years, with over 70% of cases diagnosed at the age of 30. Available data was inconclusive for trends on prevalence and there was no incidence data available for US population. Fourteen SR and eight primary studies addressed comorbid disorders. Substance use disorder was highly prevalent with alcohol abuse over 40% and drug dependence between 18% and 30.4%. Borderline personality disorders (12.5%) and anxiety disorders (65% to 86.7%), including generalized anxiety disorder (14.4% to 38.7%) and obsessive-compulsive disorders (10.7% to 24.6%) were highly prevalent and have a negative impact over the course of BD-I. We retrieved 9 SR and one primary study regarding BD-I’s staging and natural progression. Staging models identified several features in common: an earlier phase, prodromal phase, initial phase, relapsing phase and end-stage. CONCLUSIONS: BD is a chronic and disabling disease with onset in early adulthood. Knowledge on epidemiologic features may help increase awareness and early diagnosis, although there is a gap in our understanding of prevalence rates over time. Also, physicians must be attentive of the high comorbidity rates associated with BD-I.