Background: Pregnancy is a critical period that demands meticulous medical attention to ensure both maternal and fetal well-being. This study aimed to evaluate the relationship between high vaginal swab (HVS) culture results and maternal and perinatal outcomes in pregnant women attending a tertiary care hospital.Materials and Methods: This cross-sectional study was conducted on 140 pregnant women at ≥24 weeks of gestation. Participants were selected from antenatal clinics, labor wards, and emergency obstetric units. HVS samples were collected under aseptic conditions and analyzed for bacterial and fungal growth. Maternal outcomes assessed included preterm labor, premature rupture of membranes (PROM), chorioamnionitis, and postpartum endometritis. Perinatal outcomes such as preterm birth, low birth weight, neonatal sepsis, NICU admission, and perinatal mortality were recorded. Antimicrobial susceptibility testing was conducted following Clinical and Laboratory Standards Institute (CLSI) guidelines. Results: Among the 140 participants, 90 (64.29%) had a positive HVS culture, while 50 (35.71%) were culture-negative. The most commonly isolated organisms were E. coli (14.29%), Candida spp. (17.86%), and Group B Streptococcus (12.86%). Maternal outcomes were significantly worse in culture-positive women, with preterm labor (21.43% vs. 7.14%, p = 0.002), PROM (17.86% vs. 5.71%, p = 0.010), chorioamnionitis (15.71% vs. 4.29%, p = 0.008), and postpartum endometritis (12.86% vs. 3.57%, p = 0.015) occurring more frequently. Perinatal complications were also higher in culture-positive mothers, with preterm birth (16.43% vs. 7.86%, p = 0.030), low birth weight (22.86% vs. 12.14%, p = 0.017), neonatal sepsis (20.00% vs. 8.57%, p = 0.010), NICU admissions (16.43% vs. 5.00%, p = 0.004), and perinatal mortality (24.29% vs. 3.57%, p < 0.001). Antibiotic resistance analysis showed ampicillin resistance in 38.00% of isolates, whereas ceftriaxone (88.00%) and meropenem (88.00%) demonstrated the highest sensitivity.Conclusion: This study found a significant association between maternal vaginal infections and adverse pregnancy outcomes. HVS culture-positive women had a higher incidence of maternal complications, including preterm labor and PROM, as well as increased risks of neonatal complications such as preterm birth, low birth weight, and neonatal sepsis. Routine screening and early treatment of vaginal infections during pregnancy may help reduce these adverse outcomes. Additionally, antimicrobial resistance trends emphasize the importance of targeted antibiotic therapy to prevent ineffective treatments and drug resistance.