Background: There is substantial interest in the role of ginger as an adjuvant therapy for chemotherapy-induced nausea and vomiting (CINV). However, available evidence lacks robust methodology. Objective: To assess the effect of adjuvant ginger compared with placebo on chemotherapy-induced nausea-related quality of life (QoL) and CINV-related outcomes. Design: A parallel, double-blind, placebo-controlled randomized trial with 1:1 allocation was conducted. Participants/setting: One hundred three chemotherapy-naïve adults scheduled to receive moderately to highly emetogenic chemotherapy at two hospitals in Australia were enrolled and analyzed. Intervention: Four standardized ginger capsules (totaling 84 mg/day active gingerols/shogaols), or placebo, were administered commencing the day of chemotherapy and continuing for 5 days for chemotherapy cycles 1 through 3. Main outcome measures: The primary outcome was chemotherapy-induced nausea-related QoL. Secondary outcomes were vomiting- and CINV-related QoL; anticipatory, acute, and delayed nausea and vomiting; fatigue; nutritional status; depression and anxiety; health-related QoL; and adverse events. Statistical analyses performed: Intention-to-treat analysis was performed. Mixed analysis of variance with repeated measures determined differences between groups. The null hypothesis was no difference between groups. After applying a Bonferroni multiple testing correction, evidence against the null hypothesis was considered at P= 0.003. Results: One hundred three participants (ginger: n = 52; placebo: n = 51) were enrolled and analyzed. There was clinically relevant evidence against the null hypothesis, favoring ginger, in change scores for nausea-related QoL (F[df] = 9.34[1,101]; P = 0.003; partial η2 = 0.09), overall CINV-related QoL (F[df] = 12.26[1,101]; P < 0.001; partial η2 = 0.11), delayed nausea severity (F[df] = 9.46[1,101]; P = 0.003; partial η2 = 0.09), and fatigue (F[df] = 10.11[1,101]; P = 0.002; partial η2 = 0.09). There was a clinically meaningful lower incidence of delayed nausea and vomiting in the ginger group at Cycle 2 (53% vs 75%; P = 0.020 and 4% vs 27%; P = 0.001, respectively) and Cycle 3 (49% vs 79%; P = 0.002 and 2% vs 23%; P = 0.001, respectively). There was a clinically meaningful lower incidence of malnutrition in the ginger group at Cycle 3 (18% vs. 41%; P = 0.032) and in change scores for Patient-Generated Subjective Global Assessment (F[df)] = 4.32[1,100]; P = 0.040; partial η2 = 0.04). Change scores between groups favored ginger for vomiting-related QoL and number of vomiting episodes; however, findings were not clinically meaningful. There was no effect of ginger on anticipatory or acute CINV, health-related QoL, anxiety, or depression. No serious adverse events were reported. Conclusions: Ginger supplementation was a safe adjuvant to antiemetic medications for CINV that enhanced QoL during chemotherapy treatment. Future trials are needed to examine dose-dependent responses to verify optimal dosing regimens.