OBJECTIVES: To assess the hematological effects Angiotensin-converting enzyme (ACE-I) inhibitors and Angiotensin II receptor blockers (ARB) in patients without concomitant renal impairment. METHODS: In the present retrospective cohort study we used the Maccabi Healthcare Services' database to identify new users of ACE-I (N=14754) ARB (N=751), or calcium channel blockers (CCB, N=3087) with available hemoglobin (Hb) tests between 2004 and 2009. Excluded were patients purchasing drugs from more than one medication class, diagnosed with renal impairment or cancer. Median Hb levels one year before and after first medication purchase (index date) were calculated and compared according to the proportion of days covered with medication class. RESULTS: Persistent use of ACE-I and ARB was associated with a significant decrement in hemoglobin level. Patients at the highest PDC level were at a significantly higher risk of developing anemia among ACEI (OR = 1.59, p<0.001), and ARB (OR = 2.21, p=0.05). The relationship between CCB therapy and Hb decrement was substantially weaker.   CONCLUSIONS: Hb levels are reduced during the first year of ACE-I or ARB therapy. This association is dose-dependent and is not likely to be caused by artifacts related to patient adherence.