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It is important to know which factors predict the development of microalbuminuria in patients with diabetes mellitus type II.Data from the Randomized Olmesartan and Diabetes Microalbuminuria Prevention Study were used to identify predictors for the new onset of microalbuminuria. Furthermore, the interaction of baseline albuminuria and baseline estimated glomerular filtration rate (eGFR) and the effects of treatment with olmesartan were investigated.A total of 4447 patients were randomized to receive 40-mg olmesartan or placebo for a median of 3.2 years. Baseline urinary albumin–creatinine ratio (UACR) was the most important predictor of microalbuminuria, followed by age, weight, glycosylated hemoglobin type A1C, blood glucose, total cholesterol, SBP number of antihypertensive drugs and heart rate. The development of microalbuminuria was not affected by hemodynamic factors. The incidence of microalbuminuria increased from the lower to the higher UACR tertile at all baseline eGFR tertiles. The effects of olmesartan on prevention of new onset microalbuminuria were more obvious in those with the highest baseline UACR at all baseline eGFR tertiles. The eGFR declined more significantly in the olmesartan group (from 85.0 to 80.1 ml/min per 1.73 m2), whereas the decrease in the placebo group was smaller (from 84.7 to 83.7 ml/min per 1.73 m2). The highest rate of eGFR decline in the olmesartan group was in patients with the highest baseline eGFR (>95 ml/min per 1.73 m2) at all baseline UACR tertiles. The transition from normoalbuminuria to microalbuminuria in the olmesartan treated patients was not accompanied by preservation of renal function.Predictors of new onset microalbuminuria are the classical cardiovascular risk factors. Microalbuminuria development was associated with baseline UACR but not baseline eGFR, whereas eGFR decrease after introduction of olmesartan was dependent on baseline eGFR but not on baseline UACR. The effects of olmesartan on microalbuminuria development and on eGFR decrease are probably mediated by different mechanisms.Clinical Trials.gov number, NCT00185159.