This study aimed to reduce maternal anxiety scores and heart rates, increase oxygen saturation linked to vaccination processes with Skin-to skin contact (SSC). The study is a prospective, multicenter, paired, randomized, controlled trial. This experimental study was conducted with a pretest-posttest control group. The study was carried out with 128 mothers of infants. A Sociodemographic Questionnaire, the State Anxiety Inventory and a pulse oximeter were used in the data collection. In the study, SSC began to be given to the infants in the intervention group five minutes before vaccination and the infant was left in SSC for an uninterrupted 15 minutes following the vaccination. The maternal anxiety scores were noted before and after the vaccination process. The mothers' heart rates and oxygen saturation were monitored a total of three times. The anxiety scores of the intervention group decreased while oxygen saturation increased after the vaccination as compared to the control group. The heart rate decreased in the intervention group but increased in the control group. The study revealed that SSC reduced scores of maternal anxiety and heart rates and increased oxygen saturation during the vaccination process.