Background and Objective: Vaccination is the most common iatrogenic pain in healthy children that medicine should not be ignored. Therefore, any action in order to reduce the injection pain is an important part of health care. Since the order and method of vaccination may also be influenced by the experience of pain, this study aimed to determine the effect of (diphtheria, pertusis, tetanus) vaccine and Hepatitis B injection on pain response amang two-month infants in 1391, referred to health centers in Rafsanjan.Materials and Methods: The present study was a double-blind randomized controlled field trial. In this study, 160 infants aged 2 months attending Rafsanjan health centers.They are randomly divided into four groups (n= 40). In the first group, the hepatitis B vaccination was administered by standard method, the second group received the same vaccine in pragmatic method, the third group, the DPT vaccine to standard method, and the fourth group, the DPT vaccine in pragmatic method. In all groups the second vaccine was administered as the same way as the first one.Using the Modified Behavioral Pain Scale (MBPS) and a demographic information checklist, the infant’s pain responses were evaluated. Data were analyzed by SPSS18 software. To describe the data, descriptive statistics (mean and standard deviation) and ANOVA were used for statistical analysis.Results: Of the 160 infants (51.25%) were male. In terms of weight, height and duration of breast feeding prior to vaccination did not differ between groups. Mean pain scores (MBPS) in group who had first received hepatitis B vaccine in pragmatic method were significantly lower than the other groups (p<0.001).Conclusion: The results showed that pain intensity is less when hepatitis B vaccine was administered in pragmatic method. Therefore, it is recommended vaccinators having regard to the safety order vaccine that causes less pain, as well as a less painful injection method.