Preterm birth (PTB; < 37 weeks) affects ²10 % of pregnancies and is the leading cause of neonatal mortality. Whether maternal high-risk human papillomavirus (hr-HPV) infection contributes to spontaneous PTB is unsettled. Romania, with Europe’s highest cervical-cancer burden, offers a relevant setting to explore this association. We prospectively followed 151 women enrolled before 14 weeks’ gestation at a tertiary maternity hospital (January 2021–May 2022). Cervical samples were tested with the Cepheid Xpert HPV assay, which detects 14 high-risk HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68). Maternal age, parity, smoking, body mass index, and comorbidities were recorded. PTB was defined as delivery < 37 weeks (very PTB < 34 weeks). Multivariable logistic regression estimated adjusted odds ratios (aOR) for PTB associated with hr-HPV, and Kaplan–Meier curves compared time-to-delivery between infected and uninfected pregnancies. hr-HPV DNA was detected in 60/151 pregnancies (39.7 %). PTB occurred in 28.3 % of hr-HPV-positive versus 13.2 % of hr-HPV-negative women (P = 0.02); very PTB rates were 8.3 % and 2.2 %, respectively. Median gestational age and birth weight were lower among infected mothers (38.0 weeks vs 39.0 weeks, P = 0.04; 3025 g vs 3230 g, P = 0.03), while Apgar scores were comparable. After adjustment for maternal covariates, hr-HPV remained independently associated with PTB (aOR = 2.38; 95% CI 1.07–5.29; P = 0.033), and survival analysis confirmed a higher cumulative hazard of early delivery (log-rank P = 0.021). First-trimester hr-HPV carriage approximately doubled the odds of preterm birth in this Romanian cohort, independent of established risk factors. Although genotype-specific risks require confirmation, the data align with emerging evidence that HPV infection itself—not only post-treatment cervical changes—may promote spontaneous PTB. If corroborated, these findings extend the public-health value of HPV vaccination beyond cancer prevention and support closer obstetric surveillance of hr-HPV-positive pregnancies.