OBJECTIVES:  Analog insulin glulisine has a higher efficacy in reducing postprandial glucose excursions and in restoring normal postprandial microcirculation than regular human insulins. Besides glycemic control, insulin glulisine has also favorable effects in maintaining normal endothelial function. Therefore, the aim was to compare the incidence of macro- and microvascular outcomes in type 2 diabetic patients treated with insulin glulisine or regular human insulin. METHODS: Computerized data from 952 glulisine (age: 61 ± 11 yrs) and 11,157 regular insulin (65 ± 11 yrs) users in general practices throughout Germany (Disease Analyzer, 11/2004 to 3/2010) were analysed. Hazard ratios (HR; Cox regression) for 3.5-year risk of macro- or microvascular outcomes were adjusted for age, sex, diabetes duration, health insurance, residency, diabetologist care, hypertension, hyperlipidemia, depression, and co-medication (basal insulin, oral antidiabetics). Furthermore, adjustment was carried out for baseline microvascular complications when analyzing macrovascular outcomes and vice versa. RESULTS: Overall, risk for both macro- and microvascular outcomes was 20% lower for patients using insulin glulisine (p<0.05). There was a decreased risk for coronary heart disease (HR; 95% CI: 0.78; 0.62-0.99), and a trend for lower events  of myocardial infarction (0.66; 0.43-1.02). Also for microvascular complications, the adjusted hazard ratios for retinopathy, nephropathy and neuropathy were below 1.0, indicating a lower risk for the insulin glulisine group, however, which was statistically significant for neuropathy only (0.74; 0.58-0.93). CONCLUSIONS: The prescription of the rapid-acting insulin analog glulisine was associated with a reduced incidence of macro- and microvascular outcomes in type 2 diabetes under real-life conditions in a retrospective database analysis. It is important to confirm this finding in a randomized controlled trial.