Background: Integration of pharmacists into primary care general practice clinics has the potential to improve interdisciplinary teamwork and patient care; however this practice is not widespread. Objective: The aim of this study was to review the effectiveness of clinical pharmacist services delivered in primary care general practice clinics. Methods: A systematic review of English language randomized controlled trials cited in the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and International Pharmaceutical Abstracts was conducted. Studies were included if pharmacists had a regular and ongoing relationship with the clinic; delivered an intervention aimed at optimizing prescribing for, and/or medication use by, clinic patients; and were physically present within the clinic for all or part of the intervention, or for communication with staff. The search generated 1484 articles. After removal of duplicates and screening of titles and abstracts against inclusion criteria, 131 articles remained. A total of 38 studies were included in the review and assessed for quality. Seventeen studies had common endpoints (blood pressure, glycosylated hemoglobin, cholesterol and/or Framingham risk score) and were included in meta-analyses. Results: Twenty-nine of the 38 studies recruited patients with specific medical conditions, most commonly cardiovascular disease (15 studies) and/or diabetes (9 studies). The remaining 9 studies recruited patients at general risk of medication misadventure. Pharmacist interventions usually involved medication review (86.8 ), with or without other activities delivered collaboratively with the general practitioner (family physician). Positive effects on primary outcomes related to medication use or clinical outcomes were reported in 19 studies, mixed effects in six studies, and no effect in 13 studies. The results of meta-analyses favored the pharmacist intervention, with significant improvements in blood pressure, glycosylated hemoglobin, cholesterol and Framingham risk score in intervention patients compared to control patients. Conclusions: Pharmacists co-located in general practice clinics delivered a range of interventions, with favorable results in various areas of chronic disease management and quality use of medicines.