The role of vaccinations in risk of developing multiple sclerosis (MS) or in risk of relapse has not been well established. The aim of this study was to estimate the effect of immunizations on risk of developing MS in adults as well as in subsequent risk of relapse. Systematic search for publications in MEDLINE (1966-January 2011), EMBASE (1977-January 2011) and the Cochrane Central Register of Controlled Trials (CENTRAL) (1961-January 2011). Both randomized clinical trials and non-randomized studies addressing the effect of any Center for Diseases Control (CDC) recommended vaccine for children, adults or travelers and BCG on risk of MS or disease relapse were included. Two reviewers independently extracted information from articles selected using a predefined datasheet. No significant change in the risk of developing MS after vaccination was found for BCG (OR 0.96, 95% CI 0.69-1.34), Hepatitis B (OR 1.00, 95% CI 0.74-1.37), Influenza (OR 0.97, 95% CI 0.77-1.23), Measles-Mumps-Rubella (MMR) (OR 1.02, 95% CI 0.64-1.61), Polio (OR 0.87, 95% CI 0.61-1.25) and Typhoid fever (OR 1.05, 95% CI 0.72-1.53). We found decreased risk of developing MS for Diphtheria (OR 0.60, 95% CI 0.40-0.90) and Tetanus (OR 0.68, 95% CI 0.54-0.84). Influenza immunization was also associated with no change in risk of MS relapse (RR 1.24, 95% CI 0.89-1.72). Risk of developing multiple sclerosis remained unchanged after BCG, Hepatitis B, Influenza, MMR, Polio and Typhoid fever immunization, whereas diphtheria and tetanus vaccination may be associated with a decreased risk of MS. Further research is needed for the remaining vaccines.