The objective was to examine prevalence of behavioral health disorders (BHDs) and co-occurring chronic medical conditions in a 3.4 million-member integrated health system. Clinical databases identified 255,993 patients diagnosed with the most prevalent BHDs (cases): depression, anxiety, substance use, bipolar spectrum and attention deficit and hyperactivity (ADHD); non-BHD matched controls were created for all unique cases. Cases and controls were compared for prevalence of general medical conditions and specific chronic diseases and the Charlson Comorbidity Index (CMI). The five most common BHDs were depression (58%), anxiety (42%), substance use (16%), bipolar spectrum (6%) and ADHD (4%). Compared to controls, patients with depression (80.1% vs. 66.3%), anxiety (78.0% vs. 63.0%), substance use (74.0% vs. 59.9%), bipolar (75.3% vs. 60.7%) and ADHD (60.6% vs. 53.1%; all P<.001) had significantly higher prevalence of any medical comorbidities. Excluding ADHD, BHD cases had higher prevalence of selected chronic diseases and average CMI. BHDs in a largely commercially insured, employment-based health system are common and associated with a disproportionately higher burden of chronic medical disease and associated 10-year mortality risk rate. Given that co-occurrence of behavioral and medical conditions leads to elevated symptom burden, functional impairment, and healthcare costs, these findings highlight the importance of developing effective collaborative models of care in (nonpublic) employment-based health systems.