Data based on randomized clinical trials regarding intravenous thrombolysis (IVT) versus placebo or any other antithrombotic treatment in ischemic stroke (IS) due to artery dissection (AD) are not available. We used data from our observational study to examine the efficacy and safety of IVT in patients with IS due to spontaneous AD, as compared with stroke patients of the same cause who were not treated with IVT. Outcome measures were modified Rankin score (mRS) for functional outcome, death from all causes, occurrence of any intracranial hemorrhage, local signs of an intramural hematoma extension, recurrent IS, and recurrent AD. In a 4-year period, 19 of 46 patients with IS due to spontaneous AD were treated with IVT. Favorable outcome (mRS 0-2) after the follow-up period reached 81.5% of non-IVT patients compared with 94.7% of IVT-treated patients (odds ratio, 4.09; 95% confidence interval, 0.44-38.26; P=0.377). However, the patients who received IVT had a significantly higher chance of being without any neurological deficit (mRS 0) after adjusting for age, sex, baseline National Institutes of Health Stroke Scale score, and site of dissection compared with non-IVT patients after the follow-up period (P=0.012). No symptomatic intracerebral hemorrhage, worsening of local signs, cases of subarachnoid hemorrhage, or death occurred in both groups of patients. The efficacy of IVT in patients with IS due to the spontaneous AD seemed to be similar or even better to those of patients of the same cause who were not treated with IVT. The complication rate of IVT in spontaneous AD is low.