Introduction Continuous positive airway pressure (CPAP) is an initial mode of respiratory support for spontaneously breathing preterm infants in most high-income settings. It is increasingly used in low- and middle-income countries (LMICs). Bubble CPAP (bCPAP) has been extensively used worldwide for more than 30 years. The risk of death is highest in the neonatal period. An estimated 2.5 million neonatal deaths occurred globally in 2017. The leading causes of neonatal mortality; prematurity, intra-partum related causes and infections, all can lead to severe respiratory distress. Many neonatal deaths are preventable using scalable evidence- based interventions like bCPAP. Objective To assess the implementation of a multi-center comprehensive hospital-based bCPAP study in a LMIC using a low-cost bCPAP device. Methods Seven established hospitals in 3 States of the country were selected using purposive sampling. A comprehensive bCPAP program was developed and implemented using the Pumani® bCPAP device. Neonates 1000g, breathing spontaneously and neurologically viable were eligible for enrolment. Intensive workshop training was conducted for doctors and nurses working in the neonatal units on use of the device, eligible patient identification, and management. The study lasted 22 months. The planned program implementation assessment used a structured, validated questionnaire to study the progress and challenges of the study. The assessment did not evaluate or report on patient outcomes. Focus group discussions and in-depth interviews of doctors, nurses and hospital administrators were conducted by an experienced culturally-knowledgeable physician (CA). The qualitative and quantitative data were analysed and summarized. Results The low cost Pumani bCPAP device was easy to use, acceptable to staff and endorsed by both staff and patient families as effective in treatment of neonatal respiratory distress. With training, all physician and nursing staff were competent in eligible patient identification, effective set up and administration of bCPAP. The locally patented improvised bCPAP, which is widely used in the country for provision of care to neonates with respiratory problems, was in use at 50% of study sites. This resulted in some eligible patients not being treated with the Pumani bCPAP device, a study protocol deviation. All study sites experienced varying degrees of incessant electric power interruption. The worst affected hospital had <6 hours of electricity/day. Availability and affordability of oxygen was also variable across sites with only 2 sites experiencing mild to no problems. These infrastructure challenges critical to running of the device negatively impacted study implementation. Conclusion The program resulted in facility and staff capacity building. Unfortunately, the variability in essential resources such as oxygen and electricity impacted subject enrolment. This finding, underappreciated during program planning, seriously hindered the optimal program implementation hence under-utilization of this life saving technology.