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Background & Aim: Skeletal muscle contraction, secondary to pain and fear, may cause a reaction in the pelvic floor muscle contraction and may result in atypical labor progress, fetal descent and rotation of head. The object of this study was to compare the effect of acupressure at two GB-21 and SP-6 points on the severity of labor pain. Methods: In this quasi-experimental study, 150 primiparous women were randomly divided into three groups of 1-Acupressure at GB-21 point, 2-Acupressure at SP-6 point and 3-control group (contact at two points). The intervention was carried out for 20 minutes at 3-4 cm dilatation of cervix. The pain severity prior to, immediately and 3 and 60 minutes after intervention were measured by Visual Analog Scale. Collected data were analysed using repeated measures analysis of variances. Results: The pain severity before intervention among three groups was not statistically significant. Nevertheless, the pain severity was reduced immediately, 30 and 60 minutes after intervention in two intervention groups at 3-4 cm dilatation as compared with the control group (P<0.001). No significant statistical difference was observed between the two case groups (P=0.93). Conclusion: Current study showed that the application of acupressure at two GB-21 and SP-6 points was effective on the reduction of the severity of labor pain. Hence, it is recommended to conduct further studies regarding the application of acupressure along with non-medicinal methods.