Objective: The aim of this study was to perform a systematic review and meta-analysis to assess whether cerebral small vessel disease (CSVD) on neuroimaging of patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis (IVT) is associated with an increased risk of hemorrhagic transformation (HT), symptomatic intracranial hemorrhage (sICH), and poor functional outcome (PFO). Methods: A thorough search of several databases was carried out to identify relevant studies up to December 2020. We included studies of patients with AIS and neuroimaging markers of CSVD treated with IVT. The primary outcome was HT, and the secondary outcomes were sICH and 3-month PFO. The quality of the studies involved was evaluated using the Newcastle-Ottawa Scale (NOS). The meta-analysis with the fixed effects model was performed. Results: Twenty-four eligible studies (n = 9,419) were pooled in the meta-analysis. All included studies were regarded as high quality with the NOS scores of at least 6 points. The meta-analysis revealed associations between the presence of CSVD and HT, sICH, and the 3-month PFO after IVT. Compared with no CSVD, the presence of CSVD was associated with an increased risk of HT (OR: 1.81, 95% CI: 1.52-2.16), sICH (OR: 2.42, 95% CI: 1.76-3.33), and 3-month PFO (OR: 2.15, 95% CI: 1.89-2.44). For patients with AIS complicated with CSVD, compared with a CSVD score of 0-1, a CSVD score of 2-4 was associated with an increased risk of HT (OR: 3.10, 95% CI: 1.67-5.77), sICH (OR: 2.86, 95% CI: 1.26-6.49), and 3-month PFO (OR: 4.58, 95% CI: 2.97-7.06). Conclusion: Patients with AIS complicated with neuroimaging markers of CSVD are at increased risk of HT and 3-month PFO after IVT. However, it is still necessary to clarify the exact role of CSVD in the occurrence, development, and prognosis of AIS. Systematic Review Registration: www.ClinicalTrials.gov, identifier CRD4202123 3900.Copyright © 2021 Wang, Yan, Zhan, Zhang, Zhang, Ge, Wen, Wang, Xu and Lu.