We previously demonstrated that local massage for one minute can enhance immunogenicity of diphtheria, tetanus, and whole-cell pertussis (DTPw) vaccination. This study further analyzes the effects of more intense local manipulation on infants after DTPw and DTPa (diphtheria, tetanus, and acellular pertussis) vaccination. A total of 808 infants aged two months were recruited to be vaccinated with either DTPw or DTPa. Vaccinees in both groups were further divided into two groups; those receiving local manipulation (massage and hot packing after vaccinations) and those receiving only vaccinations. Results showed that safety profiles were largely similar between those who had local manipulation following vaccination and those without. The only significant difference was more frequent local reactions including pain and swelling following the first two doses in both the DTPa and DTPw groups receiving manipulation compared with the groups not receiving manipulation. Serologic tests revealed that local manipulation had no significant effect on antibody response to pertussis toxin and filamentous hemagglutinin, and diphtheria and tetanus toxins. The effect of local massage on DTPw was related to the intensity of local massage. Too vigorous a local manipulation caused adverse local reactions and no beneficial effect on antibody response. As for the infants receiving DTPa and local massages for two minutes with hot packing, no significant effect on either the reactogenicity or immunogenicity was found.