Assessment of compliance in patients with relevant comorbidity condition, above all those at high cardiovascular risk, is especially relevant because their clinical condition can be considerably mitigated by treatment with concomitant antihypertensive (AH) and lipid-lowering (LL) medications. The aim of the study was to evaluate patterns and predictors of adherence and persistence with concomitant AH and LL therapy. This retrospective cohort study included 363 enrolled from database of 3 physicians who initiated treatment with AH and LL therapy between January 2007 and January 2010. Adherence was measured as the proportion of days covered in 3-month intervals and patients were considered adherent if they had filled prescriptions for at least 80% of the period. Persistence was measured as absence of discontinuation define as > 30 days between a filled prescription and the subsequent claim. A multivariate analysis with a Cox regression model was performed to evaluate potential predictors of adherence and persistence. Finally, patients outcome was evaluated to assess potential association with adherence and persistence with AH and LL therapy. The mean percentage of patients adherent with both AH and LL medications was 39%, declining from 47% to 31%. The mean percentage of persistence was 43%. After adjustment for variables of interest, major predictors of adherence and persistence were the number of concomitant prescriptions, age of patients, gender time between start of AH and LL therapy, and gravity of coronary disease. Finally, adherent and persistent patients had significant lower blood pressure compared to other subjects. Adherence and persistence with concomitant AH and LL therapy was poor and declined over time. Interventions to improve these attitudes and to contain costs affecting a limited health budget are needed.