Background:Low-cost bubble continuous positive airway pressure (bCPAP) systems have been shown to improve survival in neonates with respiratory distress, in developing countries including Malawi. District hospitals in Malawi implementing CPAP requested simple and reliable guidelines to enable healthcare workers with basic skills and minimal training to determine when treatment with CPAP is necessary. We developed and validated TRY (T: Tone is good, R: Respiratory Distress and Y=Yes) CPAP, a simple algorithm to identify neonates with respiratory distress who would benefit from CPAP. Objective:To validate the TRY CPAP algorithm for neonates with respiratory distress in a low-resource setting. Methods: We constructed an algorithm using a combination of vital signs, tone and birth weight to determine the need for CPAP in neonates with respiratory distress. Neonates admitted to the neonatal ward of Queen Elizabeth Central Hospital, in Blantyre, Malawi, were assessed in a prospective, cross-sectional study. Nurses and paediatricians-in-training assessed neonates to determine whether they required CPAP using the TRY CPAP algorithm. To establish the accuracy of the TRY CPAP algorithm in evaluating the need for CPAP, their assessment was compared with the decision of a neonatologist blinded to the TRY CPAP algorithm findings. Results: 325 neonates were evaluated over a 2-month period; 13% were deemed to require CPAP by the neonatologist. The inter-rater reliability with the algorithm was 0.90 for nurses and 0.97 for paediatricians-in-training using the neonatologist's assessment as the reference standard. Conclusions:The TRY CPAP algorithm has the potential to be a simple and reliable tool to assist nurses and clinicians in identifying neonates who require treatment with CPAP in low-resource settings.