Objective: To study dosing frequency of metformin in relation to HbA1c-goal attainment in daily practice. Methods: Data for this nested case-control study were obtained from the PHARMO Record Linkage System, including among others linked drug-dispensing and clinical-laboratory records of approximately three million individuals in defined areas of the Netherlands. The study cohort included new users of oral glucose-lowering drugs (OGLD) between 1999-2005, with a baseline HbA1c =7% and consecutive HbA1c-measurements within 18 months. Cases attained HbA1c-goal (HbA1c <7%) within 18 months. Controls did not attain HbA1c-goal. Compliant cases and controls on metformin monotherapy were included in the analyses. Dosing frequency was dichotomized into once-daily and twice-daily or more. In the multivariate analysis we considered OGLD-dose, baseline HbA1c, prescriber and number of HbA1c-measurements. Results: The study cohort included 3107 new OGLD-users. The analyses included 753 cases and 477 controls using metformin. Dosing twice-daily or more was associated with a 71% higher probability of attaining goal (OR 1.71 (95%CI 1.31-2.24)) compared to once-daily dosing, after adjustment for baseline HbA1c and prescriber. We could not distinguish between the effect of dose and dosing frequency as these were closely related. Statistical testing in the analyses stratified by dose was prohibited by small numbers. Conclusion: About 40% of compliant metformin users were not at goal because of dosing problems. A strong correlation between total daily dose and dosing frequency did, however, not permit to identify one of these dosing items as most important attribute.