The safety and efficacy of intravenous thrombolysis (IVT) in dissection-related ischemic stroke (DRIS) has not been established. We sought to determine safety and recovery rates of IVT in DRIS using prospective, international, multicenter data and by conducting a comprehensive meta-analysis of reported case series. We analyzed consecutive DRIS patients treated with IVT according to national guidelines during a 5-year period at six tertiary-care stroke centers, and also conducted a comprehensive review and meta-analysis of all available case series reporting safety outcomes in DRIS treated with IVT according to PRISMA guidelines. A total of 39 DRIS patients (mean age 60 ± 18 years; 59 % men; median NIHSS 13 points, IQR 9–17) received IVT in our multicenter study. Symptomatic intracranial hemorrhage (sICH), in-hospital mortality, complete recanalization, favorable functional outcome (FFO; mRS-score of 0–1) and functional independence (FI; mRS-score of 0–2) were 0 % (adjusted Wald 95 % CI 0–8 %), 10 % (3–24 %), 55 % (40–70 %), 61 % (45–74 %) and 68 % (52–81 %). The pooled sICH and mortality rates in meta-analysis including 10 case series (234 IVT-DRIS patients) were 2 % (0–5 %) and 4 % (0–8 %). The pooled recanalization, FFO and FI rates were 45 % (26–67 %), 41 % (29–54 %) and 61 % (48–72 %), respectively. Substantial heterogeneity was only found for FFO (I 2 = 61 %; p = 0.006). Subsequent meta-regression analysis identified baseline NIHSS and dissection in the posterior circulation as independent predictors of FFO (p < 0.05), accounting for FFO variance across different studies. Our prospective, international data coupled with comprehensive meta-analysis results underscore IVT safety in DRIS, while further independent validation is required in larger observational registries or RCTs.