Conventional measures of gestational weight gain (GWG), such as average rate of weight gain, are likely to be correlated with gestational duration. Such a correlation could introduce bias to epidemiological studies of GWG and adverse perinatal outcomes because many perinatal outcomes are also correlated with gestational duration. This study aimed to quantify the extent to which currently used GWG measures may bias the apparent relationship between maternal weight gain and risk of preterm birth. For each woman in a provincial perinatal database registry (British Columbia, Canada, 2000-2009), a total GWG was simulated such that it was uncorrelated with risk of preterm birth. The simulation was based on serial antenatal GWG measurements from a sample of term pregnancies. Simulated GWGs were classified using three approaches: total weight gain (kg), average rate of weight gain (kg/week) or adequacy of GWG in relation to Institute of Medicine recommendations. Their association with preterm birth =32 weeks was explored using logistic regression. All measures of GWG induced an apparent association between GWG and preterm birth =32 weeks even when, by design, none existed. Odds ratios in the lowest fifths of each GWG measure compared with the middle fifths ranged from 4.4 [95% confidence interval (CI) 3.6, 5.4] (total weight gain) to 1.6 [95% CI 1.3, 2.0] (Institute of Medicine adequacy ratio). Conventional measures of GWG introduce serious bias to the study of maternal weight gain and preterm birth. A new measure of GWG that is uncorrelated with gestational duration is needed.