Background: Spontaneous rupture of membranes is a normal component of labor and delivery. Premature rupture of the membranes is defined as rupture of membranes before the onset of labor, and if it occurs before 37 weeks, it is termed preterm premature rupture of membranes. Preterm premature rupture of membranes (PPROM) is one of the major factors that have been found to correlate with adverse pregnancy outcome. It remains a critically important clinical and public health problem. Objective: To assess the prevalence and associated factor of preterm premature rapture of membrane in pregnant admitted Debre Markos Comprehensive Specialized Hospital. Methodology: Hospital based cross-sectional study was conducted in the study period. The study was conducted from April 1 to June 30 2021.Total sample size of 425 participants were involved in the study. Systematic random sampling techniques were applied to select study participants. Data was entered into EPI data version 3.1 and then exported to SPSS version 25 for analysis .Bivariable and Multivariable logistic regression used for analysis. Result: The prevalence of pre term premature rupture of membrane was found to be 14.4%. Pregnant women with abnormal vaginal discharge (AOR=2.15, 95% CI =(1.08-4.29)), urinary tract infection (AOR=2.4,95%CI=(1.24-4.66) previous history of preterm premature rupture of membrane(AOR=4.31,95%CI=(1.86-10.01)),previous history of preterm birth (AOR=3.11,95%CI=(1.29,7.48)),and mid upper arm circumference<23cm(AOR=2.99,95%CI=(1.55-5.78)) were associated with preterm premature rupture of membrane. Conclusions: The prevalence of preterm premature rupture of membrane was high. Abnormal vaginal discharge, urinary tract infection, previous preterm premature rupture of membrane, previous history of preterm birth, and mid-upper arm circumference <23cm were associated with preterm premature rupture of membrane. Recommendation: Early screening and treatment of urinary tract infections and abnormal vaginal discharges were recommended to reduce the risk of preterm premature rupture of membrane. Keywords: Premature rupture of membrane, Pre term birth, Debre Markos Comprehensive Specialized, Ethiopia.