Objective: Our aim was to investigate evening chronotype, a proxy marker of circadian system dysfunction, as a clinical subphenotype in bipolar disorder (BD)., Methods: In this cross-sectional study, 773 BD participants and 146 control subjects were evaluated using the Structured Clinical Interview for DSM-IV and a set of questionnaires. Chronotype was determined using item-5 from the reduced Morningness-Eveningness Questionnaire. Univariate analyses and regression models were used to compare evening and non-evening chronotype in BD and chronotype association with clinical variables., Results: Overall, 205 (27%) of BD patients reported an evening chronotype. Evening chronotype was higher in a matched sub-sample of BD patients (n = 150) than in controls (24% and 5% respectively, OR=5.4, p<0.01). Compared to those with non-evening chronotypes, BD patients with an evening chronotype were younger, had an earlier age of onset of BD, and had more prior depressive and manic episodes, higher rates of rapid cycling, past suicide attempts, more comorbid anxiety and substance use disorders. Multivariate regression showed age, prior suicide attempts, and co-occurring substance use disorder were associated with evening chronotype (OR range of 0.97 to1.59). Hypertension, migraine, asthma, and obstructive sleep apnea were significantly associated with evening chronotype (OR range of 1.56 to 2.0)., Limitation: Limitations include a cross-sectional study design that precludes establishing causality. Analyses did not control for medication use. Younger participant age may prevent evaluation of associations with late-life illnesses., Conclusions: Evening chronotype may be a discrete clinical subphenotype in BD and circadian dysfunction a shared pathophysiological mechanism between psychopathology and medical morbidity., Competing Interests: Declaration of Competing Interest Dr. Romo-Nava reports support from the Brain & Behavior Research Foundation NARSAD Young Investigator Award; receiving nonfinancial support from Soterix Medical outside the submitted work; and having patent 62 581 968 pending. dr. McElroy reported receiving grants and personal fees from Allergan, Avanir, Myriad, Shire, and Sunovion; receiving grants from Brainsway, Marriott Foundation, Medibio, Neurocrine, and Novo Nordisk; receiving personal fees from Bracket, F. Hoffmann-LaRoche Limited, Mitsubishi Tanabe Pharma America, and Opiant; being a consultant to or member of the scientific advisory boards of Bracket, MedAvante, Naurex, Shire, and Sunovion; being a principal or co-investigator on studies sponsored by the Agency for Healthcare Research & Quality, AstraZeneca, Cephalon, Forest, Marriott Foundation, the National Institute of Mental Health, Orexigen Therapeutics Inc, Shire, and Takeda Pharmaceutical Company Ltd; being an inventor on US Patent 6 323 236 B2; and receiving payments from Johnson & Johnson, which has exclusive patent rights. dr.. Frye reported receiving grants from the Marriott Foundation during the conduct of the study; receiving grants from the National Institute of Alcohol Abuse and Alcoholism and National Institute of Mental Health, National Institutes of Health, Assurex Health, Myriad, and Pfizer; being a consultant to Janssen Global Services LLC; receiving other support from Mitsubishi Tanabe Pharma Corporation, Myriad, Sunovion, and Teva Pharmaceuticals; receiving travel and hotel honoraria from CME Outfitters to give a lecture for continuing medical education credit and receiving support for a presentation from Sunovion. No other disclosures are reported., (Copyright © 2020 Elsevier B.V. All rights reserved.)