To determine the effects of a personal health record (PHR)-linked medications module on medication accuracy and safety.From September 2005 to March 2007, we conducted an on-treatment sub-study within a cluster-randomized trial involving 11 primary care practices that used the same PHR. Intervention practices received access to a medications module prompting patients to review their documented medications and identify discrepancies, generating 'eJournals' that enabled rapid updating of medication lists during subsequent clinical visits.A sample of 267 patients who submitted medications eJournals was contacted by phone 3 weeks after an eligible visit and compared with a matched sample of 274 patients in control practices that received a different PHR-linked intervention. Two blinded physician adjudicators determined unexplained discrepancies between documented and patient-reported medication regimens. The primary outcome was proportion of medications per patient with unexplained discrepancies.Among 121,046 patients in eligible practices, 3979 participated in the main trial and 541 participated in the sub-study. The proportion of medications per patient with unexplained discrepancies was 42% in the intervention arm and 51% in the control arm (adjusted OR 0.71, 95% CI 0.54 to 0.94, p=0.01). The number of unexplained discrepancies per patient with potential for severe harm was 0.03 in the intervention arm and 0.08 in the control arm (adjusted RR 0.31, 95% CI 0.10 to 0.92, p=0.04).When used, concordance between documented and patient-reported medication regimens and reduction in potentially harmful medication discrepancies can be improved with a PHR medication review tool linked to the provider's medical record.This study was registered at ClinicalTrials.gov (NCT00251875).