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Introduction Preterm birth, defined as birth < 37 completed weeks of gestation, is a complex syndrome and remains a major global public health problem (Goldenberg et al. 2008; Muglia and [...], BACKGROUND: Although effects of weather changes on human health have been widely reported, there is limited information regarding effects on pregnant women in developing countries. OBJECTIVE: We investigated the association between maternal exposure to ambient temperature and the risk of preterm birth (< 37 weeks of gestation) in Guangzhou, China. METHODS: We used a Cox proportional hazards model to estimate associations between preterm birth and average temperature during each week of gestation, with weekly temperature modeled as a time-varying exposure during four time windows: 1 week (the last week of the pregnancy), 4 weeks (the last 4 weeks of the pregnancy), late pregnancy (gestational week 20 onward), and the entire pregnancy. Information on singleton vaginal birth between 2001 and 2011 was collected. Daily meteorological data during the same period were obtained from the Guangzhou Meteorological Bureau. RESULTS: A total of 838,146 singleton vaginal births were included, among which 47,209 (5.6%) were preterm births. High mean temperatures during the 4 weeks, late pregnancy, and the entire pregnancy time windows were associated with an increased risk of preterm birth. Compared with the median temperature (24.4°C), weekly exposures during the last 4 weeks of the pregnancy to extreme cold (7.6°C, the 1st percentile) and extreme heat (31.9°C, the 99th percentile) were associated with 17.9% (95% CI: 10.2, 26.2%) and 10.0% (95% CI: 2.9, 17.6%) increased risks of preterm birth, respectively. The association between extreme heat and preterm birth was stronger for preterm births during weeks 20-31 and 32-34 than those during weeks 35-36. CONCLUSIONS: These findings might have important implications in preventing preterm birth in Guangzhou as well as other areas with similar weather conditions. http://dx.doi.org/10.1289/ehp.1509778