OBJECTIVES: To investigate comorbidities associated with glaucoma and trend of glaucoma incidence in the California Medicaid population. METHODS: A retrospective case-control study was conducted using 20% sample of the Medi-Cal administrative claims data from January 1, 1995 to December 31, 2002. Patients with glaucoma were identified using ICD-9 diagnosis (ICD-9=365.xx) and were 1:3 randomly matched to a cohort without glaucoma based on age and gender. Eligibility was measured by the number of enrollment months. Relative risk (RR) was calculated to estimate the risk of glaucoma patients to a profile of 25 comorbidities set forth by AHRQ. RESULTS: A total of 32,395 glaucoma patients were matched to 97,185 controls. The mean age was 65.5 (+/-19.8) and 34.9% were male. Over the eight years of study period, glaucoma patients had significantly longer length of Medi-Cal eligibility than non-glaucoma patients (71.6 vs. 50.8 months, p<0.0001). African Americans were at significantly higher risk of glaucoma (RR=1.53) and Hispanics had lower risk (RR=0.74). Patients with glaucoma were at significantly higher risk for most diseases, such as rheumatoid arthritis (RR=1.49), hypothyroidism (RR=1.39), diabetes (RR=1.35), valvular diseases (RR=1.35), depression (RR=1.32) and peripheral vascular diseases (RR=1.26). The yearly incidence rate for glaucoma decreased over time from 48.5 per 10,000 person-year in 1995 to 18.6 per 10,000 person-year in 2002. The average incidence rate for glaucoma patients was 29.0 per 10,000 person-year during the eight-year study duration. CONCLUSIONS: The glaucoma population suffers from numerous comorbidities, although it is not clear whether they affect treatment alternatives. The incidence rate of glaucoma sharply declined from 1995 to 2002 in Medi-Cal population.