Background and Purpose— Intravenous thrombolysis with alteplase is approved for acute ischemic stroke, but its use is limited by numerous contraindications and warnings arising from trial selection criteria or expert opinions. We examined outcomes from alteplase-treated versus untreated patients, registered in a trials archive, according to presence or absence of specified contraindications and warnings. Methods— We analyzed 90-day modified Rankin Scale across the whole distribution of scores using the Cochran–Mantel–Haenszel test, with adjustment for age and baseline National Institutes of Health Stroke Score, followed by proportional odds logistic regression analysis to estimate the odds ratios for preferred outcome. Results— We used data from 9613 ischemic stroke patients of whom 2755 were treated with thrombolysis. Adjusted odds ratios showed a broad trend of more favorable 3-month outcome associated with alteplase treatment versus no treatment in various subgroups of patients with contraindications and warnings; for example, 1.40 (95% confidence interval [CI], 1.14–1.70) in patients aged >80 (n=1805), 1.50 (95% CI, 1.03–2.18) in patients with combined history of prior stroke and diabetes mellitus (n=672), 1.42 (95% CI, 1.19–1.70) in patients on prior single antiplatelet agent (n=1626), 2.20 (95% CI, 1.12–4.32) in patients on oral anticoagulation, and International Normalized Ratio≤1.7 (n=157), 1.50 (95% CI, 1.15–1.97) in patients with baseline glucose >180 (n=879), and 1.57 (95% CI, 1.12–2.18) in patients with pretreatment National Institutes of Health Stroke Score >22 (n=620). Conclusions— This comprehensive retrospective analysis of various contraindications and warnings provides reassurance about benefits and risks of intravenous alteplase treatment in common clinical situations.