Background: The present study aimed to determine the association between pregnancy-associated plasma protein A (PAPP-A) and Gestational Diabetes Methods (GDM) to detect a risk factor for predicting GDM at gestational weeks 11-14. Methods: This analytical prospective study recruited 284 pregnant women presenting to six healthcare centers of Qazvin, Iran from February to December 2016. PAPP-A was measured at gestational weeks 11-14 and glucose tolerance test was conducted at gestational weeks 24-28. The participants were assigned into two groups of exposure (reduced PAPP-A) and non-exposure (normal PAPP-A). The association between GDM and PAPP-A was studied. The number of women in exposure group were 201 and 83 in the non-exposure group. Differences between groups were assessed by the Mann–Whitney, Chi-square, T test, logistic regression analysis and ROC Curve with a significance level of 0.05. Results: Twenty eight (33.73%) patients of the exposure group and 17 (8.46%) of non-exposure group developed GDM. There was a significant difference between the two groups in terms of GDM (p<0.001) and the risk of GDM was 3.98 fold higher in the exposure group (reduced PAPPA mu/L) than that of the non-exposure group (CI=2.39-6.65, p<0.001). Also, 53.3% of the exposure group and 46.7% of the non-exposure group were diagnosed with GDM (p=0.02). There was a significant difference in GDM between the groups and the risk of GDM was 1.85 times higher in the exposure group (reduced PAPPA MOM) than that in the control group (CI=1.09-3.15, p=0.020). According to the ROC curve results, PAPP-A and MOM are acceptable indicators for predicting GDM. Conclusion: A low PAPP-A level (MOM, MU/L) as a new risk factor for GDM can help early prediction and prevent maternal and fetal complication by timely treatment.