Background: Preterm Premature Rupture of Membranes (PPROM) is a significant obstetric complication associated with adverse maternal and neonatal outcomes. Identifying early hematological markers could aid in risk prediction and preventive strategies. This study investigates the association between Mean Platelet Volume (MPV) and Platelet Count (PC) measured at 11–13 weeks of gestation with the risk of PPROM. Methods: This prospective cohort study was conducted at the Department of Fetomaternal Medicine and Obstetrics and Gynecology, Bangabandhu Sheikh Mujib Medical University (BSMMU), from September 2022 to August 2023 included 73 pregnant women who underwent MPV and PC measurement at 11–13 weeks of gestation. Participants were monitored until delivery for PPROM occurrence. Diagnostic efficacy was assessed using Receiver Operating Characteristic (ROC) curve analysis, and risk estimation was performed using relative risk (RR) calculations. Results: PPROM occurred in 9 out of 73 participants (12.3%). A significantly lower MPV (≤8.0 fL) was observed in 77.8% of PPROM cases compared to 6.3% in the non-PPROM group (p<0.001), with a relative risk (RR) of 19.73. The combination of high PC (≥294,000/cu.mm) and low MPV (≤8.0 fL) was present in 44.4% of PPROM cases versus 4.7% in the non-PPROM group (p=0.003), with an RR of 7.54. ROC analysis showed that MPV had an AUC of 0.856, with 77.8% sensitivity, 93.8% specificity, 98.9% positive predictive value (PPV), and 37.2% negative predictive value (NPV), indicating a stronger predictive value than PC. Conclusion: MPV measured at 11–13 weeks of gestation is a strong predictor of PPROM, with better diagnostic accuracy than PC. The combination of low MPV and high PC further strengthens this association. Early screening using MPV may help identify high-risk pregnancies, allowing for closer monitoring and timely interventions.