Post-stroke depression (PSD) is a frequent problem in stroke rehabilitation. Several studies have evaluated association between the lesion location and the risk of depression. Different conclusions and contradictory findings have been published. The aim of the present study was to perform a systematic meta-analysis to evaluate the relationship between PSD and lesion location. We researched PubMed, ISI Web of Science, EMBASE, and systematically reviewed available publications reporting investigations on stroke location and risk of PSD. Subgroup analyses were performed according to the time since stroke onset to assessment for PSD or the source of patients. Odds ratios (ORs) and 95 % confidence intervals (CIs) were used for pooled analyses. Heterogeneity was assessed with Cochran's Q test and I (2) test. Begg's funnel plot and Egger's test were used to examine the publication bias. A total of 43 studies involving 5,507 patients suffering from stroke were included in this meta-analysis. The pooled OR with 95 % CI for the overall association of stroke location and depression risk was 0.99 (0.88-1.11). Subgroups analyses highlighted that only studies with subacute post-stroke group (1-6 months) showed a statistical association between right hemisphere stroke and risk of depression (OR = 0.79, 95 % CI 0.66-0.93). This systematic review offered no support for the hypothesis that lesion of the left hemisphere was associated with an increased risk of depression after stroke. We only find significant association between right hemisphere stroke and incidence of depression for studies within subacute post-stroke phase.