Objective: To evaluate respiratory morbidity (RM) in HIV-exposed newborns according to mode of delivery. Methods: The NISDI Perinatal/LILAC prospective cohort studies enrolled HIV-infected pregnant women and their newborns in Latin America and the Caribbean. Associations between RM and delivery mode or other characteristics were evaluated. Results: Between September 2002 and December 2009, 1630 women were enrolled, and 1443 mother-infant pairs met the inclusion criteria. There were 561 vaginal (VD), 269 cesarean before labor and membrane rupture (SCS) for preventing mother-to-child transmission (SCS-PMTCT), 248 other SCS, and 365 cesarean after labor and/or ruptured membranes (NSCS) deliveries. In total, 108 (7.5%) newborns had RM: 49 had respiratory distress syndrome (RDS), 39 had transient tachypnea (TTN), and 28 had other events (7 newborns had > 1 RM event). Delivery mode was associated with RDS (P < 0.005) and TTN (P < 0.001). The proportion with RDS and TTN was lowest for VD (1.6% and 0.5%, respectively), highest for NSCS (4.9% and 4.7%), and intermediate for SCS-PMTCT (3.0% and 2.6%). Newborns with RDS or TTN were hospitalized longer (median + 1 day) than those without. A minority required ventilatory support (RDS, 24.5%-28.6%; TTN, 2.6%-15.4%). Conclusions: SCS-PMTCT is relatively safe for newborns of HIV-infected women. © 2011 International Federation of Gynecology and Obstetrics.