Leukemia is the most commonly diagnosed childhood cancer, although its etiology is still largely unknown. Growing evidence supports a role for infection in the etiology of acute lymphocytic leukemia (ALL), and the involvement of the immune system suggests that vaccination may also play a role. However, the findings presented in the published literature are inconsistent. Therefore, we conducted a PRISMA systematic review and meta-analysis. 14 studies were identified and meta-analyzed. Vaccinations studied comprised Bacillus Calmette-Guérin (BCG) vaccine, Triple vaccine, Hepatitis B vaccine (HBV), Polio, Measles, Rubella, Mumps, trivalent MMR vaccine and Haemophilus influenza type B (HiB) vaccine. We observed a protective association between any vaccination in the first year of life and risk of childhood leukemia (summary odds ratio (OR) 0.58 [95% confidence interval (CI) 0.36-0.91]). When individual vaccines were analysed, some evidence of an association was seen only for BCG (summary OR 0.73 [95% CI 0.50-1.08]). In conclusion, early vaccination appears to be associated with a reduced risk of childhood leukemia. This finding may be underpinned by the association observed for BCG. Given the relatively imprecise nature of the results of this meta-analysis, our findings should be interpreted cautiously and replicated in future studies.