Effects of lifestyle change on blood glucose levels can be monitored by self-monitoring of blood glucose (SMBG) in type 2 diabetes mellitus (T2DM) patients. We analyzed whether the SMBG-structured lifestyle intervention program ROSSO-in-praxi-international can improve glucometabolic control in the short and the long term. One hundred twenty-four SMBG-naive ambulatory non-insulin-treated T2DM patients were randomly assigned to an SMBG group (n=63) and a control group (n=61). Both groups received a 12-week structured lifestyle guidance manual. The SMBG group additionally got a blood glucose meter with 150 test strips and was instructed to measure blood glucose regularly as well as event-driven. Glucometabolic parameters were assessed at baseline, after 12 weeks, and after 1.5 years. During the 12 weeks of intervention the SMBG group significantly improved glycated hemoglobin (HbA1c) levels (from 7.4 ± 1.6% to 6.9 ± 1.1% [P<0.001]) and weight (-0.9 ± 1.9 kg [P<0.05]), whereas HbA1c reduction (from 7.5 ± 1.0% to 7.3 ± 1.0%) and weight loss (-0.6 ± 2.4 kg) were not significant in the control group. Of the 124 patients, 122 completed the 1.5-year follow-up. In the control group HbA1c increased again, reaching baseline values (7.5 ± 0.7%). In the SMBG group HbA1c remained stable (6.9 ± 0.9% [P=0.0003 for trend]), and weight (-1.6 ± 3.0 kg vs. baseline [P=0.0003 for trend]) improved further. Eighty-seven percent of participants in the SMBG group continued to perform SMBG. Those who measured their blood glucose more than three times per week (n=24) demonstrated an overall reduction in HbA1c of 1.0% (P=0.006 vs. three times or fewer per week) after 1.5 years. Integration of SMBG into basic therapy of T2DM for monitoring the effect of lifestyle changes improves glucometabolic control and has long-term effects.