Vaccination against hepatitis B virus (HBV) is the most cost-efficient measure to prevent infection. Still, vaccination coverage among adults in Central Asia, including Kyrgyzstan, remains suboptimal, and data about immune responses to HBV vaccination are lacking. HBV vaccination is given as three injections, whereby the second and third doses are given 1 and 6 months after the first (0-1-6 scheme). However, compliance with the third dose is low in Kyrgyzstan, presumably due to the long time interval between the second and third doses, suggesting that a shortened vaccination schedule could result in better adherence and increased seroconversion. Thus, we conducted a randomized trial of individuals aged 17–66 years comparing the 0-1-6 scheme against a shorter 0-1-3 scheme. Primary outcome measures were post-vaccination titers and the percentage of participants with protective post-vaccination titers (≥10 mIU/mL). Compliance with the completeness of blood draws and administered third vaccine dose was better with the 0-1-3 scheme than with the 0-1-6 scheme. In both study arms combined, younger age (<40 years) was associated with better vaccine protection. The 0-1-6 scheme resulted in higher post-vaccination titers (52 versus 15 mIU/mL, p = 0.002) and a higher seroprotection rate (85% versus 64%, p = 0.01) than the 0-1-3 scheme, whereby post-vaccination titers correlated negatively with age in the 0-1-3 scheme. Thus, the 0-1-6 scheme should continue to be the preferred HBV vaccination schedule, but interventions to improve compliance with the third vaccine dose are needed.