Objective: Recurrent miscarriage (RM) is one of the most common clinical problems in reproduction. The aims of the current study were to evaluate the expression of ERK and Akt pro- teins in human trophoblastic tissue and to assess the significance of MAPK and PI3K-Akt signal pathways in the progression of unexplained recurrent miscarriage. Study design: A case-control study. Setting: Women Health Hospital, Assiut, Egypt. Materials and methods: All pregnant women presented with first-trimester inevitable miscarriage with a history of RM, defined as three or more spontaneous consecutive first-trimester miscarriages before 12 weeks’ gestation, were included in the study (RM group). Age-matched healthy women who had at least one normal pregnancy with no history of miscarriage were included as a control group at the time of delivery. A sample of trophoblastic tissue was taken for Western blot test to evaluate the level of phospho-ERK and Akt (active forms) proteins in trophoblastic tissue. Results: The study included 20 women in each group. There were non-significant differences between both groups as regards maternal age, BMI, passive smoking and family residence. There were significantly lower levels of p-ERK and p-Akt in the RM group as compared to the control group ( p = 0.001). Conclusion: The activation of ERK and Akt pathway plays a significant role in RM. The data suggest that decreased expression of p-ERK and p-Akt occurs less frequently during RM may play a role in this process. This suggests that p-ERK and p-Akt may be markers of RM Expression of ERK and Akt proteins in women with unexplained first-trimester recurrent miscarriage. Available from: https://www.researchgate.net/publication/308780788_Expression_of_ERK_and_Akt_proteins_in_women_with_unexplained_first-trimester_recurrent_miscarriage [accessed Oct 2, 2016].