OBJECTIVE To assess whether exposure to standing, lifting, night work, or long work hours during 3 periods of pregnancy are associated with an increased risk of preterm or small-for-gestational-age birth. METHODS The Pregnancy, Infection and Nutrition study is a prospective cohort with a nested case-control component that was conducted through clinic and hospital settings in Central North Carolina. A total of 1,908 women pregnant with a singleton gestation were recruited during prenatal visits from January 1995 through April 2000 and provided information during telephone and face-to-face interviews about physical exertion for the 2 longest-held jobs during pregnancy. RESULTS No significant elevations in preterm delivery were observed among women who lifted repeatedly or stood at least 30 hours per week, with no changes in risk estimates over the course of pregnancy. A 50% elevation in the risk of preterm delivery (relative risk 1.5, 95% confidence interval 1.0-2.0; first trimester) was observed among women who reported working at night (10:00 PM to 7:00 AM), whereas a 40% reduction in risk was observed among women working at least 46 hours per week (relative risk 0.6, 95% confidence interval 0.4-0.9; first trimester), regardless of period of exposure. No elevations in small-for-gestational-age birth were observed among women exposed to any of the 4 types of occupational exertion. CONCLUSIONS Physically demanding work does not seem to be associated with adverse pregnancy outcomes, whereas working at night during pregnancy may increase the risk of preterm delivery. Studies to examine the effect of shift work on uterine activity would help to clarify the possibility of a causal effect on preterm birth.