Background: Women who had gestational diabetes mellitus (GDM) in their first pregnancy are prone to having it again in a second pregnancy. Even women who did not have GDM in their first pregnancy may still be susceptible to developing it in a second pregnancy. Identifying the factors that increase the likelihood of recurrent or new occurrent GDM is important for improving the planning of future pregnancies. Methods: A total of 759 multiparous women, tested for GDM in two consecutive pregnancies, were retrospectively enrolled (Endocrinology Unit, Catanzaro, Italy). GDM was diagnosed by IADPSG criteria using 75g OGTT. To compare clinical features and glucose levels from 75g OGTT, performed at 24-28 weeks and/or earlier in case of a former GDM diagnosis, women were divided into four groups: 1) 493 NGT women at both pregnancies; 2) 74 women with a new occurrence of GDM at their second pregnancy; 3) 92 women with non-recurrent GDM at their second pregnancy; 4) 100 women with recurrent GDM at their second pregnancy. Results: Intergroup comparisons revealed the clinical predictors of GDM at the first pregnancy (family history of type 2 diabetes, PCOS, early menarche, advanced maternal age, pregravid obesity), at the second pregnancy (interpregnancy BMI gain) and of recurrent GDM (pregravid obesity, PCOS). A positive correlation was observed between the 75g OGTT glucose levels of consecutive pregnancies. Adjusted logistic regression analysis showed that higher level of 1h-postload glucose (ROC optimal cut-point: 130 mg/dL) at the first gestational 75g OGTT would enhance the likelihood of a new occurrence of GDM in a second pregnancy (aOR 2.50, 95%CI 1.51-4.13), whereas higher levels of 2h-postload glucose (ROC optimal cut-point: 153 mg/dL) at the first diagnostic 75g OGTT would enhance the likelihood of GDM recurrence (aOR 2.21, 95%CI 1.06-4.63). Conclusions: Clinical risk factors, and their dynamic changes throughout female reproductive life span, as well as postload glucose levels at first gestational 75g OGTT can serve as predictors of GDM in multiparous women. This information can be used to tailor preventive interventions, such as interpregnancy weight loss.