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Background: Based on World Health Organization guidelines, Government of India recommended management of possible serious bacterial infection (PSBI) in young infants up to two months of age on an outpatient basis where referral is not feasible. We implemented the guideline in program setting to increase access to treatment with high treatment success and low resultant mortality. Methods: Implementation research was conducted in four rural blocks of Lucknow district in Uttar Pradesh, India. It included policy dialogues with the central and state government and district level officials. A Technical Support Unit was established. Thereafter, capacity building across all cadres of health workers in the implementation area was done for strengthening of home based newborn care (HBNC) program, skills enhancement for identification and management of PSBI, logistics management to ensure availability of necessary supplies, monitoring and evaluation as well as providing feedback. Data was collected by the research team. Results: From June 2017 to February 2019 there were 24,448 live births in a population of 856106. We identified 1302 infants, aged 0–59 days, with any sign of PSBI leading to a coverage of 53% (1302/2445), assuming an incidence of 10%. However, in the establishment phase the coverage was 33%, while it was 85% in the implementation phase. Accredited social health activists (ASHAs) identified 81.2% (1058/1302) cases while rest were identified by families. ASHAs increased home visits within first 7 days of life in home based newborn care program from 74.3% (2781/3738) to 89.0% (3128/3513) and detection of cases of PSBI from 1.6% (45/2781) to 8.7% (275/3128) in the first and last quarter of the project, respectively. Of these 18.7% (244/1302) refused referral to government health system and 6.7% (88/1302) were treated in a hospital. Among cases of PSBI, there were 13.3% (173/1302) cases of fast breathing in young infant aged 7–59 days in whom referral was not needed. Of these 147 were treated by oral amoxicillin and 95.2% (140/147) were cured. Among those who needed referral, simplified treatment was given when referral was refused. There were 2.9% (37/1302) cases of fast breathing at ages of 0–6 days of which 34 were treated by simplified treatment with100% (34/34) cured;66.5% (866/1302) were cases of clinical severe infection of which 685 treated by simplified treatment with94.2% (645/685)cured and 09 died;17.3% (226/1302) cases of critical illness of which 93 were treated by simplified treatment, as a last resort, 72% (67/93) cured and 16 died. Among 255 cases who either did not seek formal treatment or sought it at private facilities, 96 died. Conclusion: Simplified treatment for PSBI is feasible in public program settings in northern India with good cure rates. It required system strengthening and supportive supervision. [ABSTRACT FROM AUTHOR]