BACKGROUND: The aim of this study was to assess the association between prescription changes frequency (PCF) and hospital admissions and to compare the PCF to the Chronic Disease Score (CDS). The CDS measures comorbidity on the basis of the 1-yearharmacy dispensing data. In contrast, the PCF is based on prescription changes over a 3-month period. METHODS: A retrospective matched case-control design was conducted. 10.000 patients were selected randomly from the Dutch PHARMO database, who had beenhospitalized (index date) between July 1, 1998 and June 30, 2000. The primary study outcome was the number of prescription changes during several three-month time periods starting 18, 12, 9, 6, and 3 months before the index date. For each hospitalized patient, one nonhospitalized patient was matched for age, sex, and geographic area, and was assigned the same index date as the corresponding hospitalized patient. We classified four mutually exclusive types of prescription changes: change in dosage, switch, stop and start. RESULTS: The study population comprised 8,681 hospitalized patients and an equal number of matched nonhospitalized patients. The odds ratio of hospital admission increased with an increase in PCF category. At 3 months before the indexdate from PCF=1 OR 1.4 [95% CI 1.3-1.5] to PCF= 2-3 OR 2.2 [95% CI 1.9-2.4] and to PCF >/= 4 OR 4.1 [95% CI 3.1-5.1]. A higher CDS score was also associated with an increased odds ratio of hospitalization: OR 1.3 (95% CI 1.2-1.4) for CDS 3-4, and OR 3.0(95% CI 2.7-3.3) for CDS 5 or higher. CONCLUSION: The prescription change frequency (PCF) is associated with hospital admission, like the CDS. Pharmacists and other healthcare workers should be alert when the frequency of prescription changes increases.Clinical rules could be helpful to make pharmacists and physicians aware of the risk of the number of prescription changes.