Background: Low birth weight (LBW) is an important public health problem. The problem is prevalent world-wide and has negative impacts. So, its prevention is a major challenge. Objective: To determine maternal risk factors of LBW in Cairo city. Design: A case-control, hospital-based, study design. Subjects: Mothers of 270 LBW neonates were recruited in this study. A control group of mothers of an equal number of normal birth weight (NBW) neonates was chosen. Methods: The mothers of LBW and NBW neonates were interviewed using a specially designed questionnaire. All mothers had been subjected to full examinations. The neonates were weighted and examined after labor. Results: Low education, unskilled occupation, and husband unavailability are significant sociodemographic risk factors of LBW; OR=1.75, 1.62, and 2.21, respectively. Mother's height (≤145 cm), BMI (<18 kg/m²), history of previous abortion, and maternal family history of LBW are significant personal characteristic risk factors of LBW; OR=3.26, 5.11, 3.27, and 3.23, respectively. The significant obstetric risk factors are congenital malformations, weight gain during pregnancy ≤6 kg, multiple gestations, bleeding at first/second trimester, presence of complications during delivery, gestation age <37 weeks, and birth spacing <2 years; OR=13.61, 7.61, 7.15, 5.92, 3.93, 3.17, and 2.84, respectively. Absence of antenatal care, inadequate healthy diet intake, physical hard activities, exposure to tobacco smoke, and living nearby heavy air pollution are significant health care behavioral and life-style risk factors of LBW; OR=2.49, 2.72, 2.96, 3.64, and 4.8, respectively. Anemia, hypertension, and history of recurrent chronic/specific infections are significant medical risk factors of LBW; OR=2.68, 4.35 and 4.84, respectively. Anorexia nervosa/stress, oligo/polyhydramnios, and gestational hypertension are significant gynecological/obstetric conditions risk factors; OR=3.53, 3.32, 3.23, and 3.36, respectively. Lastly, the most important risk factors of LBW as weighted by partial F-test are multiple gestations, neonate congenital malformations, weight gain during pregnancy ≤6 kg, maternal BMI <18 kg/m², gestation age <37 weeks, and mother's weight at early pregnancy ≤45 kg, (F test=2.9, 2.7, 2.6, 2.3, 2.2, and 2.2, respectively).  Recommendations: There is a need for improving the quality and utilization of ANC services, nutritional education, birth spacing, and avoidance exposure to tobacco smoke. Also, increasing promotion of reproductive health services in relation to safe motherhood at community level in order to reduce risk factors of LBW is needed. Lastly, further population based studies are needed in different areas in Egypt.