Background: Theophylline was an orally administered xanthine used for the treatment of apnea of prematurity and Bronchopulmonary Dysplasia in the ambulatory follow-up of Low-Birth-Weight infants (LBWI) with oxygen-dependency in the Kangaroo Mother Care Program (KMCP). Theophylline’s main metabolic product is caffeine; therefore, it was an alternative due to the frequent lack of ambulatory oral caffeine in low and middle-income countries. Purpose: to assess the effectiveness of oral Theophylline in decreasing days with oxygen and to describe frequency of adverse related events. Method: quasi-experiment before and after withdrawal of Theophylline given systematically to LBWI with ambulatory oxygen in two KMCPs. Results: 729 patients were recruited; 319 with Theophylline and 410 after Theophylline withdrawn. The Theophylline cohort had less gestational age, less weight at birth, more days in Neonatal Intensive Care Unit, more days of oxygen-dependency at KMCP admission, and more frequencies of Intrauterine Growth Restriction and apneas. After adjusting with propensity score matching, multiple linear regression was done, and analysis showed that nutrition had a greater effect on days of oxygen-dependency than the fact of receiving Theophylline. No differences were found in readmissions up to 40 weeks, nor in the frequency of intraventricular hemorrhage or neurodevelopmental problems. The Theophylline group had more tachycardia episodes. Conclusions: we did not find evidence of oral Theophylline effect on the reduction of days of oxygen-dependency. For the current management of oxygen- dependency in newborns, the importance of KMCPs nutritional protocols based on exclusive breast feeding whenever possible, is the challenge for these fragile infants.