Background: Acupressure is known to be a nursing intervention used to prevent chemotherapy-induced nausea and vomiting in children. Methods: This study was conducted to evaluate and compare the effectiveness of manual and wristband acupressure in the prevention of chemotherapy-induced nausea and vomiting in children. This double-blinded and placebo-controlled study was conducted with 44 children aged between 5 and 18 years receiving chemotherapy in a university hospital's pediatric oncology clinic. Children were randomized into groups using a 2 × 2 factorial design: (a) The child who was given manual acupressure before the first chemotherapy was given placebo manual acupressure before the next chemotherapy; (b) the same child who was administered wristband acupressure before the first chemotherapy was administered placebo wristband acupressure before the next chemotherapy. After all interventions, the severity and number of episodes of nausea and vomiting and additional antiemetic needs in the children were monitored for 24 h. Results: In both groups, the severity and number of nausea and vomiting were lower according to their own placebo groups. Manual and wristband acupressure were effective in reducing the severity and number of nausea and vomiting, but manual acupressure was more effective in reducing the severity and number of nausea and vomiting in comparison to wristband acupressure (p < .05). No statistically significant difference was found between the groups regarding additional antiemetic drug use. Discussion: In this study, manual and wristband acupressure were determined to be effective in reducing the severity and number of nausea and vomiting related to chemotherapy.