Background Vascular dementia (VaD) is the most severe manifestation of cognitive impairment caused by cerebrovascular disease. There are currently no specific drug treatments approved for VaD, with cholinesterase inhibitors (AChEI) being frequently used in VaD. However, the benefits they provide are small and short-lived. The standardized extract of Ginkgo biloba EGb 761 has demonstrated protective properties against neuronal and vascular damage and has been used as a pharmacological treatment for VaD. Objectives This study aims to study the efficacy of EGb 761 alone and in combination with AChEI in a real-life setting. We carried out a retrospective analysis of data over a 12-month period in a sample of people suffering from VaD. Methods We retrospectively identified 77 patients with a diagnosis of VaD who had received treatment with any of the following drugs: Ginkgo biloba extract EGb 761 (240 mg daily), donepezil (10 mg daily), galantamine (16 or 24 mg daily), or rivastigmine patch (9.5 or 13.3 mg daily). Subjects were divided into three groups according to the treatment they had received: EGb 761 alone (n = 25), AChEI alone (n = 26), and EGb 761+AChEI (n = 26). Cognitive functioning was assessed by Mini-Mental State Examination (MMSE), Rey Auditory Verbal Learning Test (RAVLT), Symbol Digit Modalities Test (SDMT), Boston Naming Test (BNT), Trail Making Test forms A (TMTA) and B (TMTB), Letter (LFT) and Category Fluency Test (CFT); neuropsychiatric symptoms were assessed by the Neuropsychiatric Inventory (NPI); functional capacity was assessed by Interview for Deterioration in Daily Living (IDDD).Results A statistically significant improvement was observed in the EGb 761 group versus the AChEI group at 12 months' follow-up in CFT (+1.74, p < 0.001), TMTA (−17.91, p = 0.031) and NPI (−5.89, p < 0.001). With regard to the combined treatment, a statistically significant improvement was shown in the EGb 761 plus AChEI treatment group versus AChEI group at the 12-month follow-up in MMSE (+2.0, p = 0.001), RAVLT (+2.23, p = 0.007), CFT (+1.15, p = 0.013), TMTA (−19.92, p = 0.012), TMTB (−46.50, p < 0.001) and NPI (−6.77, p < 0.001). In the same line, a statistically significant improvement was observed in the EGb 761 plus AChEI treatment group versus EGb 761 at 12-month follow-up regarding MMSE (+2.11, p = 0.001), RAVLT (+2.35, p = 0.004) and TMTB (−25.25, p = 0.015). Conclusion After 12 months of treatment EGb 761 alone or combined with AChEI showed cognitive and behavioral benefits in patients suffering from VaD. This study thus provides additional real-world evidence for the combined use of EGb 761 and anti-dementia drugs in VaD patients.