Although research suggests that mail order pharmacy use is associated with greater medication adherence and cardiovascular disease risk factor control, no research has examined the potential impact of mail order pharmacy use on patient safety and utilization. To compare safety and utilization outcomes in patients using mail order versus local pharmacies. Cross-sectional, observational study of 17,217 Kaiser Permanente Northern California adult diabetes patients prescribed new cardiometabolic medications in 2006. Multivariate logistic regressions assessed the association between mail order pharmacy use and all-cause and preventable hospitalizations and emergency department (ED) visits; laboratory tests for monitoring persistent medications; and overlapping days of supply of contraindicated medications. Results were stratified by patient age and converted to adjusted predicted percentages. Patients aged less than 65 years using mail order had fewer ED visits (33.8% vs 40.2%; P <.001); preventable ED visits (7.7% vs 9.6%; P <.01); and serum creatinine laboratory monitoring tests after angiotensin-converting enzyme inhibitor/angiotensin receptor blocker or diuretic initiation (41.2% vs 47.2%; P <.01). Among patients aged 65 or more years, mail order users had fewer preventable ED visits (13.4% vs 16.3%; P <.01); but slightly more occurrences of overlapping days of supply of contraindicated medications (1.1% vs 0.7%; P <.01). Mail order pharmacy use is not associated with adverse outcomes in most diabetes patients, and is associated with lower ED use. Interventions to increase mail order pharmacy use should use a patient-centered approach that is sensitive to primary and preventive care access.