Introduction: Studies have shown in vitro fertilization (IVF) treatment to have a significant impact on women's quality of life. In addition, anxiety is experienced during IVF treatment and prior to knowing the outcome from a treatment cycle. Although support services are available at many IVF clinics, the uptake of these opportunities may not be high. Acupuncture is used by women undertaking IVF treatment in the belief that it improves their reproductive outcomes, and some studies suggest that it may reduce anxiety. The objective of this study was to examine the effects of acupuncture compared with sham acupuncture on quality of life and anxiety for women undergoing an IVF cycle. Material and methods: A multicenter randomized controlled trial was conducted in Australia and New Zealand. Women were eligible if they were aged 18-42 years, undergoing a fresh IVF cycle and not using acupuncture. Recruitment occurred between June 2011 and October 2015. Women were randomized to acupuncture or a sham acupuncture control group and three treatments were administered, the first treatment between day 6 and 8 of ovarian stimulation, and two treatments were given on the day of embryo transfer. The primary outcome was livebirth. Secondary outcomes included quality of life and anxiety, and were assessed at baseline, on the day of embryo transfer and 14 weeks from trial entry. Results: In all, 848 women were randomized to the trial, 608 women underwent an embryo transfer, of which 526 (86%) received all three treatments. Adjusted analysis found that women receiving acupuncture reported reduced anxiety following embryo transfer (mean difference [MD] −1.1, 95% CI −2.2 to −0.1, P = 0.03). Unadjusted analysis of quality of life did not differ between groups following embryo transfer. Adjusted analyses by per protocol found a significant positive change for the acupuncture group for the general health MOS Short Form 36 (SF36) domain (MD 2.6, 95% CI 0.5-4.7, P = 0.01) following embryo transfer. The benefit was not sustained at 14 weeks (MD 0.1, 95% CI −2.7 to 2.9). Conclusions: Acupuncture may reduce anxiety at embryo transfer. Quality of life did not differ between the groups. Women experience reduced emotional well-being 3 months following the IVF cycle, highlighting ongoing unmet psycho-social needs.