In order to investigate the clinical impact of home oxygen use for care of premature infants, we compared the follow-up courses after neonatal intensive care unit (NICU) discharge between very low birth weight infants (VLBWIs) with and without home oxygen. We retrospectively identified 1,232 VLBWIs born at 22 to 32 weeks of gestation, discharged from the NICU of 43 hospitals in Korea between April 2009 and March 2010, and followed them up until April 2011. Clinical outcomes, medical service uses, and readmission and death rates during follow-up after the NICU discharge were compared between VLBWIs with (HO, n = 167) and those without (CON, n = 1,056) home oxygen at discharge. The HO infants comprised 13.7% of the total VLBWIs with significant institutional variations and showed a lower gestational age (GA) and birth weight than the CON infants. The HO infants had more frequent regular pediatric outpatient clinic visits (12.7 ± 7.5 vs. 9.5 ± 6.6; P < 0.010) and emergency center visits related to respiratory problems (2.5 ± 2.2 vs. 1.8 ± 1.4; P < 0.010) than the CON infants. The HO infants also had significantly increased readmission (adjusted hazard ratio [HR], 1.60; 95% confidence interval [CI], 1.25-2.04) and death risks (adjusted HR, 7.40; 95% CI, 2.06-26.50) during up to 2 years following the NICU discharge. These increased readmission and death risks in the HO infants were not related to their prematurity degree. In conclusion, home oxygen use after discharge increases the risks for healthcare utilization, readmission, and death after NICU discharge in VLBWIs, regardless of GA, requiring more careful health care monitoring during their follow-up.