Aged Care Assessment Teams (ACATs) in Australia assess the care needs of frail older people. Despite being at high risk of medication-related problems (MRPs), ACAT patients do not routinely receive a comprehensive medication review. The aims of the study were to compare three methods for facilitating a pharmacist-led comprehensive medication review for people referred to an ACAT, and compare MRPs identified via ACAT usual care with those identified via pharmacist-led medication reviews. A prospective, randomized, comparative study involving 80 community-dwelling patients (median age 84 years) referred to an ACAT in Melbourne, Australia, was conducted. Following ACAT assessment (usual care), a clinical pharmacist reviewed all participating patients' ACAT files to identify potential MRPs not identified by the ACAT (medication review method 1). Patients were then randomized into two groups. Group A received information about the Australian government-funded, general practitioner (GP)-initiated Home Medicines Review (HMR) programme, and a letter was sent to their GP recommending an HMR (GPHMR; medication review method 2). Group B patients were referred directly to a clinical pharmacist associated with the ACAT for an ACAT-initiated pharmacist home medicines review (APHMR; medication review method 3); the pharmacist arranged a home visit, obtained a thorough medication history and conducted a comprehensive medication review. The main outcome measures were the proportion of patients who received a pharmacist home visit within 28 days; the number of MRPs identified by ACAT usual care, pharmacist review of ACAT files, and APHMR, and their clinical risk (assessed by a geriatrician-pharmacist panel); and patients', GPs' and ACAT clinicians' opinions about pharmacist medication review. Three hundred patients were referred to the ACAT, and 80 were recruited into the study. Thirty-six of 40 APHMR patients (90.0%) received a pharmacist home visit within 28 days, compared with 7/40 GPHMR patients (17.5%).[p < 0.001]. Twenty-one MRPs were identified via ACAT usual care. Pharmacist review of ACAT files identified a further 164 potential MRPs (median 2.0 per patient; inter-quartile range [IQR] 1.0-3.0); however, in patients who received an APHMR, 35/82 potential MRPs (42.7%) turned out not to be actual problems, most commonly because of discrepancies between the patient's ACAT medication list and the medications currently being used by the patient (median 3.0 discrepancies per patient; IQR 2.0-5.5). APHMR identified a further 79 MRPs (median 2.0; IQR 1.0-3.0). One hundred and twenty-two MRPs were included in APHMR reports sent to patients' GPs. Of these, 94 (77.0%) were assessed as being associated with a moderate, high or extreme risk of an adverse event. Sixty-four APHMR recommendations (52.5%) led to changes to patients' medication regimens or medication management. Thirty-six of 39 GPs (92.3%) who provided feedback reported that pharmacist medication reviews were useful. Patients (or their carers) also reported that pharmacist home visits were useful: median rating 4.25 out of 5 (IQR 4.0-5.0). Seven of 11 ACAT clinicians (77.8%) agreed that pharmacist-led medication review should be a standard component of ACAT assessments. ACAT assessments without pharmacist involvement detected fewer MRPs than any of the evaluated pharmacist-led medication review methods. APHMR was more effective than pharmacist review of routinely collected ACAT data, and more reliable and timely than referral to the patients' GP for a GPHMR.