The currently recommended intradermal regimen for post-exposure prophylaxis spreads over a month period which many times lead to low compliance from the patients. There is a need to introduce and evaluate short course regimens to overcome this problem. This study was conducted to evaluate the immunogenicity and safety of a “new one week intradermal regimen” for rabies post-exposure prophylaxis. A total of 80 healthy adult volunteers were enrolled and allocated randomly either to purified chick embryo cell (PCECV) rabies vaccine or purified verocell rabies vaccine (PVRV), 40 in each group. Each subject received intradermally one of the vaccines, using the one week regimen (4–4-4). Blood samples were collected on Days 0, 7, 14, 28,180 and 365 for estimation of rabies virus neutralizing antibody (RVNA) concentration. The sera samples were analyzed by rapid fluorescent focus inhibition test (RFFIT). All subjects in both the groups had adequate RVNA concentration of ≥ 0.5 IU/mL from day 14 to till day 180 and the difference of geometric mean concentrations between the two groups was not significant (p > 0.606). Further to assess the immunological memory produced by this new regimen, a “single visit four site” intradermal booster vaccination was given to those who did not have adequate RVNA concentration on day 365. This resulted in a quick and enhanced RVNA concentration in these subjects thus denoting a successful anamnestic response. The incidence of adverse events was 8.3% in PCECV group and 1.6% in PVRV group (p = 0.001) and the regimen was well tolerated without any dropouts. In conclusion, the new “one week intradermal regimen” is immunogenic and safe for rabies post-exposure prophylaxis and needs to be further evaluated in persons exposed to rabies.