Objective: From 40% to 65% of patients with bipolar disorder are estimated to have diagnoses of one or more comorbid conditions. The purpose of this study was to identify comorbid disorders and compare their prevalence in hospitalizations of persons with or without bipolar disorder. Methods: Data from the 1979-2006 National Hospital Discharge Survey (NHDS) were analyzed to examine temporal trends in the proportional morbidity of bipolar disorder, demographic characteristics, and the most frequent comorbid conditions in hospitalizations of patients with or without bipolar disorder. Among discharges of patients ages 13-64, the conditions of those with a primary diagnosis of bipolar disorder (N=27,054) were compared with those with other primary diagnoses (N=2,325,247). Proportional morbidity ratios (PMRs) were calculated. Results: There was an average 10% (p<.001) increase per year in the proportion of discharges with bipolar disorder. Proportions of discharge records that noted bipolar disorder were higher among females and whites and were highest among persons ages 13-19 and those from the Northeast. Discharge records noting a primary diagnosis of bipolar disorder showed higher proportions of most psychiatric and some general medical conditions, including acquired hypothyroidism (proportional morbidity ratio=2.6), viral hepatitis (1.6), obesity (1.4), and various diseases of the skin and subcutaneous tissue (range 2.6-4.2) and of the nervous (1.4-3.8), respiratory (1.4-2.3), and musculoskeletal (1.2-1.9) systems. Conclusions: Patients with bipolar disorder have an increased illness burden from many psychiatric and general medical conditions. Knowledge of the most prevalent comorbid conditions and methods for their prevention, early diagnosis, and treatment are critical in improving the prognosis of patients with bipolar disorder.