Background. Premature rupture of membranes (PROM) is associated with increased maternal and neonatal morbidities and mortalities. These include placental abruption, preterm births and its sequelae, cord prolapse and neonatal and maternal infections. It is therefore important to ensure an accurate diagnosis of PROM for appropriate management. Aim. To determine the diagnostic efficacy of vaginal fluid urea and creatinine in the diagnosis of premature rupture of membranes (PROM). Design: A prospective case control study. Setting: The study was conducted at the Department of Obstetrics and Gynaecology, University of Ilorin Teaching Hospital, Ilorin. Study population: Pregnant women at 28-42 weeks of gestation with history of liquor drainage without associated uterine contractions while controls were gestational age matched pregnant women without history of drainage of liquor. Methods: A total of one hundred and twenty eight pregnant women at 28-42 weeks of gestation were recruited for the study. Group I consisted of sixty four consenting pregnant women with PROM while the remaining sixty four participants served as controls (group II). They all had nitrazine test done on the fluid/swab from the posterior fornix. Also, all the participants had the posterior fornix irrigated with 5ml of sterile water and 3ml was aspirated and sent to the laboratory for urea and creatinine measurement. The findings were compared between the two groups to determine the diagnostic efficacy of vaginal fluid urea and creatinine in the diagnosis of PROM.