A needleless or needle-free jet injector (NFJI) uses a high-pressure stream jet to puncture the skin surface without using a needle. NFJIs have been used for vaccine or drug administration worldwide for many decades. The scope of the use of NFJIs has been continuously widened. NFJIs can be used for intradermal, subcutaneous or intramuscular injection. In the literature, NFJIs are also termed as needleless injector, jet injector (JI), disposable syringe jet injector (DSJI) in different countries by different manufacturers. In this document, the terms of NFJI, needleless injector, JI, DSJI are interchangeable. The NFJI’s operating mechanisms, applications, efficacy and safety have been constantly evolving and improving over the years. The commonly used NFJIs are PharmaJet injector (PharmaJet, USA), Med-Jet H4 injector (the newest model of Med-Jet injector, MIT Canada), Biojector (Bioject Medical Technologies Inc. USA) and LectraJet (LectraJet, D’Antonio Consultants International, Inc., USA). NFJIs have been suggested to be the future of vaccine administration and therapeutic applications. Comparing traditional (standard, conventional) needle and syringe (N-S) intramuscular injection, one of the advantages of using NFJI by intradermal injection is dose-sparing for vaccination. A typical example of the dose-sparing is that NFJIs for intradermal injection have been used, as dose-sparing strategies for the inactivated polio vaccine (IPV) in developing countries. In addition, NFJIs are preferred by individuals with an aversion to needles. Compared with N-S, other potential benefits by using NFJIs include reduced risks such as needle-stick injury and cross-contamination. However, the NFJIs are also reportedly associated with a higher frequency of local injection site reactions than the use of N-S. Effective dose-sparing strategies for vaccine delivery may be useful for large scale vaccination programs or in situations of limited vaccine supply. One suggested strategy is to administer vaccines using NFJIs by intradermal route. The purpose of this report is to review the comparative clinical effectiveness of vaccines administered using a NFJI with that using N-S for individuals of all ages.