Purpose: Limited research has assessed change in adherence status with multiple-drug regimens longitudinally. This study determined: 1) adherence rates and transition probabilities; and 2) the factors associated with transition from full adherence to lower adherence for a population with combination use of antihypertensive (AH) and lipid-lowering (LL) medications. Method: California Medicaid administrative data from 1995 through 2004 were used to identify patients ≥40 years of age with hypertension and a prescription for both an AH and LL medication. Proportion of days covered (PDC) defined three adherent classifications: fully (FA, PDC≥0.80), partially (PA, 0.2≤PDC<0.8), and non-adherent (NA, PDC<0.20). Annual transition matrices documented the probability of adherence status changes. Results: Mean (SD) age of the 8,277 patients was 64.3(11.2) years. About 14% were FA to both drugs at year 1, with 60% probability to maintain the status at year 2. 31% of patients were PA to both AH and LL, with 26% probability to maintain the status in year 2. Less than 20% of the patients were PA to one drug and FA to the other drug, with 30% probability transition to FA for both drugs. Patients who were non-adherent to LL but adherent to AH had higher probabilities (59% FA, 71% PA) than those non-adherent to AH but adherent to LL (3% FA, 48% PA, P<0.0001) of transitioning to the NA category for both drugs. Patients non-adherent to both drugs in the first year had an 83% probability for maintaining NA status. Logistic regression results show African American (OR=1.5), not having dual eligibility (OR=1.3), and initiating therapy with gemfibrozil (OR=1.3), lovastatin (OR=1.3), or niacin (OR=1.8) were significantly associated with a transition from FA to NA at year 2. Conclusion: Patients who were FA with both drugs at baseline were more likely to maintain their adherence status. Patients partially adherent to one and fully adherent to another were more likely to transition to FA in both drugs. However, those who were non-adherent for one or both drugs at year 1 had the highest probability of maintaining or transitioning to non-adherence with both drugs. Moreover, race, dual eligibility status, and type of LL medication may have significant impact on transitioning from FA to NA status. These findings will be useful in future cost effectiveness analyses incorporating adherence estimates.