Background: Preterm birth (PTB) is a major cause of infant death globally. The rising rates of pre-pregnancy diabetes mellitus (D), obesity (O) and chronic hypertension (H) will place a significant burden on maternal-fetal health but their combined influence on PTB is unknown.Methods: Population-based cohort study, Ontario, Canada, April 1, 2012 to March 31 2016. Participants were 506,483 women with a singleton livebirth or stillbirth at > 20 weeks' gestation. The exposures of interest were D, O and H, individually, and in various combinations. The primary outcome was PTB at 241/7 to 366/7 weeks. PTB was further analyzed by spontaneous or provider-initiated, early (< 34 weeks) or late (34-37 weeks), and the co-presence of preeclampsia, large for gestational age (LGA), and small for gestational age (SGA) birthweight. Multivariable Poisson regression models with robust error variance were used to generate relative risks (RR), further adjusted for maternal age and parity (aRR). Population attributable fractions were then calculated for each of the outcomes by exposure state.Findings: Relative to women without D or O or H, the aRR for PTB were (3.09, 95% CI 2.80-3.40) with D + O, 6.34 (95% CI 5.15-7.81) with D + H, 2.96 (95% CI 2.70-3.24) with O + H, and 5.55 (95% CI 4.76-6.47) with D + O + H. In women with D + H, aRR was more pronounced for provider-initiated PTB (10.99, 95% CI 8.40-14.38) than for spontaneous PTB (3.05, 95% CI 1.92-4.85). Those with D + O + H had an aRR of 9.21 (95% CI 4.97-17.04) for PTB with an SGA newborn relative to those without D or O or H.Interpretation: Combinations of D, O and H significantly magnify the risk of PTB, especially provider-initiated PTB, and PTB with altered fetal growth or preeclampsia. These data may inform health policy and clinical decision-making both at the population and patient level.Funding: CIHR.Declaration of Interest: All authors report no conflict of interestEthical Approval: Ethics approval was obtained from the St. Michael’s Hospital Research Ethics Board (REB # 16-345).