Background Mothers are frequently the first to observe the onset of jaundice in their newborn infants before the decision to seek treatment. However, simple-to-use tools that could facilitate early detection of jaundice and assist mothers to seek professional care, especially after hospital discharge, are rare. This study therefore, set out to evaluate the performance of a -two-color icterometer (Bilistrip™) as a possible screening tool for detecting significant jaundice by mothers or care-givers in the first week of life. Methods Prior to discharge, mothers in a maternity hospital were trained to use the Bilistrip™ on the blanched skin of their baby’s nose to ascertain absence (Light Yellow) or presence (Dark Yellow) of significant jaundice. Their babies had transcutaneous bilirubin (TcB) measurements independently, along with total serum bilirubin (TSB) if indicated. The reliability of Bilistrip™ as a screening test for significant jaundice was determined at different TcB and TSB thresholds. The predictive performance of Bilistrip™ was also evaluated with multivariable logistic regression. Results Some 2492 mother-infant pairs were enrolled over 15 months, of which 347 (13.9%) chose Dark Yellow. The mean TcB for Dark Yellow (10mg/dL) was significantly higher (p<0.001) than for Light Yellow (6.1mg/dL). Bilistrip™ showed increasing sensitivity (47.0% - 92.6%) and negative predictive value (NPV) (91.4% - 99.9%) for selected TcB thresholds (10mg/ dL, 12mg/dL, 15mg/dL, and 17mg/dL). Among neonates with TSB measurements (n = 124), Bilistrip™ was associated also with increasing sensitivity (86.8% - 100%) and NPV (62.5% - 100%). The sensitivity and NPV for detecting neonates requiring phototherapy were 95.8% respectively. Only one of the 24 neonates who required phototherapy was missed by the Bilistrip™. Conclusions Bilistrip™ is a potential decision-making tool for empowering mothers to detect neonates with clinically significant jaundice that may require close monitoring or treatment, and neonates not requiring treatment for jaundice in the first week of life.