Background: The integrity of collateral circulation is a major prognostic factor in ischemic stroke. Patients with good collateral status have larger penumbra and respond better to intravenous thrombolytic therapy. High systolic blood pressure is linked with worse clinical outcome in patients with acute ischemic stroke treated with intravenous thrombolytic therapy. We studied the effect of different blood pressure parameters on leptomeningeal collateral circulation in patients treated with intravenous thrombolytic therapy (<3 h) in a retrospective cohort. Methods: Anterior circulation thrombus was detected with computed tomography angiography and blood pressure was measured prior to intravenous thrombolytic therapy in 104 patients. Baseline clinical and imaging information were collected. Group comparisons were performed; Collateral Score (CS) was assessed and entered into logistic regression analysis. Results: Fifty-eight patients out of 104 displayed good collateral filling (CS ≥2). Poor CS was associated with more severe strokes according to National Institutes of Health Stroke Scale (NIHSS) at arrival (16 vs. 11, p = 0.005) and at 24 h (15 vs. 3, p < 0.001) after the treatment. Good CS was associated with higher systolic blood pressure (p = 0.03), but not with diastolic blood pressure (p = 0.26), pulse pressure (p = 0.20) or mean arterial pressure (p = 0.07). Good CS was associated with better Alberta Stroke Program Early CT Score (ASPECTS) in 24 h follow-up imaging (p < 0.001) and favorable clinical outcome at three months (mRS ≤2, p < 0.001). Median CS was the highest (CS = 3) when systolic blood pressure was between 170 and 190 mm Hg (p = 0.03). There was no significant difference in the number of patients with good (n = 11) and poor (n = 12) CS who received intravenous antihypertensive medication (p = 0.39) before or during the thrombolytic therapy. In multivariate analysis age (p = 0.02, OR 0.957 per year, 95% CI 0.92-0.99), time from the onset of symptoms to treatment (p = 0.005, OR 1.03 per minute, 95% CI 1.01-1.05), distal clot location (p = 0.02, OR 3.52, 95% CI 1.19-10.35) and systolic blood pressure (p = 0.04, OR 1.03 per unit mm Hg, 95% CI 1.00-1.05) predicted good CS. Higher systolic blood pressure (p = 0.049, OR 0.96 per unit mm Hg, 95% CI 0.93-1.00) and pulse pressure (p = 0.005, OR 0.94 per unit mm Hg, 95% CI 0.90-0.98) predicted unfavorable clinical outcome at three months in multivariate analysis. Conclusion: Moderately elevated systolic blood pressure is associated with good collateral circulation in patients treated with intravenous thrombolytic therapy. However, there is an inverse association of systolic blood pressure with the three-month clinical outcome. Diastolic blood pressure, mean arterial pressure and pulse pressure are not statistically and significantly associated with collateral status.