An association between recovery of Ureaplasma urealyticum (UU) from the respiratory tract in VLBW infants (≤1500 gm BW) and later chronic lung disease (CLD: O2 requirement and chest radiographic[CXR] changes at 28 d, or respiratory death at >7 but <28 d with consistent CXR changes) was reported by several authors before routine use of exogenous surfactant (SURF). To assess if this relation persists with routine SURF, we studied 105 VLBWs who required mechanical ventilation at<2 hrs age. Infants with major anomalies or whose mothers received antibiotics effective against UU <72 hrs from birth were excluded. Tracheal aspirates for UU culture were obtained before SURF and antibiotic therapy. Clinicians were unaware of UU status. No infant received anti-UU antibiotics. CXR at ≈28 d were reviewed by a single pediatric radiologist, blinded to UU status. Sample size was predetermined to detect a 30% increase in CLD among those with UU+ tracheal cultures (assuming 20% CLD among UU- and a 33% rate of UU+ among VLBWs) with α <0.05 and β <0.80. Of the study infants, 22 were UU+ and 83 UU-. No differences were found between UU+ and UU- groups for BW, GA, gender, inborn, antenatal or postnatal steroids, SURF therapy, non-UU infection, NEC, or PDA. At 28 d, UU+ were significantly more likely to have CLD than UU- (15/22 [68%] v 30/83 [36%]; P<0.02). UU+ also required significantly longer courses of supplemental oxygen (median 37 v 24 d: P<0.02) and mechanical ventilation (median 26 v 10 d; P<0.02). However, no significant differences were found for duration of hospitalization(56.2 ± 23.2 v 62.2 ± 19.1 d) or CLD at 36 wks postconception(6/22 [27%] v 18/83 [22%]). These findings support respiratory tract UU as a marker for high risk of CLD at 28 d and longer requirement for respiratory support, but not necessarily for CLD at 36 wk postconception or longer hospitalization. Controlled trials of anti-UU therapy in UU+ VLBWs as soon after birth as possible may determine if CLD and duration of respiratory support may be decreased, but even if successful, may not necessarily result in decreased duration and cost of hospitalization.