This study was undertaken to compare the immunogenicity and reactogenicity of two vaccines based on the attenuated Oka-strain of Varicella zoster virus (VZV), in adolescents and young adults. One hundred and eighty-six subjects, aged 13 to 29 years, were randomized to one of two groups to receive a one- or a two-dose VZV vaccine. Pre- and post-vaccination blood samples were assayed for VZV-specific IgG. Solicited local and general symptoms, as well as unsolicited symptoms, were recorded post-vaccination. Seroconversion rates were 94.9% in the one-dose, and 100% in the two-dose, regimen. The two-dose vaccine elicited significantly higher geometric mean antibody titer, 392.5 vs 86.8 pfu. Transient local injection site pain was the most frequently-reported symptom per dose in both groups (one dose: 48.9%; two-dose: 32.8%). The two-dose vaccine regimen afforded the advantage of higher antibody titers and potential increased protection from disease, without significantly increased reactogenicity.