In the acute phase of ischemic stroke, the trend of some physiological variables, such as blood glucose (BG), blood pressure, and body temperature (BT), might influence outcome. We aimed to assess the association of hyperglycemia, systolic and diastolic hypertension, and hyperthermia relative to baseline BG, systolic blood pressure, diastolic blood pressure and BT, respectively, in the first 12 h with poor outcome after intravenous thrombolysis (IVT). We conducted a retrospective analysis of data prospectively collected from 200 consecutive anterior ischemic stroke patients treated with IVT. Outcome measures were no neurological improvement at 24 h (National Institutes of Health Stroke Scale (NIHSS) score at 24 h ≥NIHSS score at baseline), and unfavorable functional outcome [modified Rankin Scale (mRS) score 3–6] at 3 months. No neurological improvement at 24 h was noted in 52 (26%) patients and mRS 3–6 at 3 months in 68 (34%) patients. The multivariate analyses showed that odds ratios (ORs) for no neurological improvement at 24 h were higher in patients with hyperglycemia relative to baseline [OR 3.50, 95% confidence interval (CI) 1.43–8.57, P = 0.006], and hyperthermia relative to baseline (OR 2.88, 95% CI 1.20–6.91, P = 0.018). OR for 3-month mRS score 3–6 was higher in patients with hyperthermia relative to baseline (OR 3.05, 95% CI 1.20–7.74, P = 0.019). Hyperglycemia and hyperthermia relative to baseline in the first 12 h after IVT are associated with no neurological improvement at 24 h. Hyperthermia relative to baseline is also associated with unfavorable functional outcome at 3 months.