OBJECTIVES: Self-monitoring of blood glucose (SMBG) may improve diabetes management. We analyzed the effect of SMBG on glycemic control, clinical outcomes and health care costs among insulin-users diabetic patients in a clinical practice setting. METHODS: A retrospective analysis using data from the administrative databases,  clinical registries containing laboratory results and medical devices databases including SMBG strips data of two Italian Local Health Units was performed. Insulin-users were defined if they had at least one prescription of insulin agents from November, 2009 and April, 2011. The first prescription was selected as index-date. Patients were divided into two groups based on testing frequency of SMBG during the 18 months after the index-date: no test strip claims (no SMBG use) and more than two test strips per day. We calculated incidence rates to estimate the risk  for fasting blood glucose levels < 70 mg/dl and for diabetes-related hospitalizations or death occurrence during the 18-months follow-up period. Total annual costs included hypoglycemic therapy and the direct costs due to diabetes-related hospitalizations and outpatient services. RESULTS: We identified 394 insulin-users patients with no SMBG use and 1350 with SMBG performed more than twice per day. Compared with non-SMBG use group, patients using SMBG showed a significant reduced risk of glucose levels < 70 mg/dl (unadjusted rate was 10,6 vs 27,3 per 100 person-years, p<0.001) and of diabetes-related hospitalizations or death (30,0 vs 60,8 per 100 person-years, p<0.001). The higher hospitalization rate resulted in higher hospitalization costs per patient (€2.419 vs €1.512 of those with SMBG use) and consequently higher total annual direct costs per patient (€3.060 vs €2.738 of those using SMBG). CONCLUSIONS: Results indicate that patients using SMBG, compared with non-SMBG patients, are associated with better glycemic control and reduced risk of diabetes-related hospitalizations and consequently with lower overall total annual cost per patient.