Objective: To compare the relative risks of 12 serious co-existing health conditions among employees with insomnia, gastroesophageal reflux disease (GERD), hepatitis C (HCV), multiple sclerosis (MS), or chronic constipation (CC). Methods: A 2001-2007 US employee database was used to identify subjects with insomnia, GERD, HCV, MS, or CC. For each condition, controls were matched on demographics, job-information, and geography. For each employee, 12-month post-index date medical claims were assigned to 261 Agency for Healthcare Research and Quality (AHRQ) condition categories using ICD-9 codes. Prevalence of these conditions was compared between the five pairs of matched disease/non-disease cohorts. Results: Numbers of employees with disease and matched employees without disease were: Insomnia 17,230/17,230; GERD 11,653/116,530; HCV 1,329/26,580; MS 765/15,300; CC 1,215/29,160. Of the 261 AHRQ categories, insomnia employees had significantly higher prevalence than controls in 201 and significantly lower prevalence in two categories. Numbers of categories with higher/lower prevalence in the GERD, HCV, MS, and CC populations compared to their respective controls were 197/7, 126/0, 96/0, and 148/0, respectively. Relative risks of coronary atherosclerosis among employees with insomnia, GERD, HCV, MS, or CC (relative to employees without these diseases) were 1.8*, 2.2*, 1.3*, 1.7*, and 1.6*, respectively. Similarly, respective relative risks were calculated for essential hypertension (1.5*, 1.6*, 1.2*, 1.1, 1.3*), hyperlipidemia (1.6*, 1.8*, 0.9, 1.2*, 1.7*), acute cerebrovascular disease (3.4*, 2.3*, 0.9, 7.8*, 2.5*), diabetes without complications (1.4*, 1.4*, 1.5*, 0.9, 1.2), diabetes with complications (1.3*, 1.3*, 1.9*, 0.9, 1.5*), chronic obstructive pulmonary disease (2.0*, 2.0*, 1.7*, 1.4, 1.4*), asthma (2.1*, 2.5*, 1.3, 1.1, 1.6*), rheumatoid arthritis (2.0*, 2.1*, 2.5*, 1.8, 2.9*), osteoarthritis (2.2*, 2.1*, 1.6*, 1.3, 1.8*), osteoporosis (1.7*, 1.7*, 1.4, 2.6*, 2.3*), and neoplasms (1.4*, 1.8*, 1.5*, 1.4*, 2.0*) (*P<0.05). Conclusion: Employees with insomnia, GERD, HCV, MS, or CC have many more serious co-morbidities than employees without these diseases.