Intravenous (i.v.) recombinant tissue plasminogen activator (rt-PA) improves outcome in ischaemic stroke, despite an increased risk of symptomatic haemorrhagic transformation (sHT). A higher baseline serum glucose concentration is associated with an increased risk of sHT. However, as most studies did not exclude diabetic patients, this effect may be partially due to diabetic micro-angiopathy. Our objective was to test the hypothesis that baseline serum glucose concentration is associated with sHT in non-diabetic patients treated by i.v. rt-PA. We analysed the influence of baseline serum glucose concentrations on sHT (ECASS2 definition) in consecutive non-diabetic patients treated by i.v. rt-PA for ischaemic stroke. Secondary end-points were death (<7days, 8days to 3months, all deaths <3months), and unfavourable outcome at 3months (modified Rankin scale 2-6 if different from the pre-stroke value). Five hundred and five consecutive patients met inclusion criteria [242 men (47.9%); median age 71years (interquartile range, IQR) 57-81; median baseline national institutes of health stroke scale score 12 (IQR 6-17)]. Thirty-seven had sHT (7.3%). After adjustment, baseline serum glucose concentrations were independently associated with sHT (adjOR: 1.176 for 1mmol/l increase; 95% CI: 1.020-1.357: p=0.025). Increased admission serum glucose concentrations in non-diabetic patients treated by i.v. rt-PA for cerebral ischaemia are associated with sHT. Whether lowering serum glucose lowers the risk of sHT needs to be evaluated.