Fertility challenges are a personal and important part of a woman’s reproductive health and are associated with health and lifestyle factors. Limited data exist on infertility among women in Palau. We describe the lifetime prevalence of self-reported infertility in a nationally representative sample of women in Palau and investigate the association between tobacco and/or betel nut use and infertility. During May-December 2016, a population-based survey of noncommunicable diseases was conducted in Palau using a geographically stratified random sample of households (N=2409). Men and women ≥18 years of age were chosen randomly from each selected household. The prevalence of a self-reported lifetime episode of infertility (having tried unsuccessfully to become pregnant for ≥12 months) was evaluated among 874 women aged ≥18 years by key health and lifestyle factors. Prevalence ratios (PR) and 95% confidence intervals (CI) were calculated. Of 315 women who ever tried to become pregnant, 39.7% (95% CI: 34.2%, 45.3%) reported a lifetime episode of infertility. Prevalence was higher in women of Palauan vs other ethnicity (PR=1.6, 95% CI: 1.1, 2.3), those who self-reported poor/not good vs. excellent/ very good health status (PR=2.1, 95% CI: 1.4, 3.3), and those with a body mass index (BMI) ≥30 vs <30 (PR=1.7, 95% CI: 1.3, 2.2). Adjusted models showed that tobacco and/or betel nut users were almost twice as likely to report infertility versus non-users (PR=1.8, 95% CI: 1.3, 2.5). More research is needed to understand the infertility experiences of women in Palau and to promote lifestyle factors contributing to optimal reproductive health.©Copyright 2020 by University Health Partners of Hawai‘i (UHP Hawai‘i).