Objective This study was conducted to determine the effect of reiki and acupressure on pain, anxiety, and vital signs during femoral sheath removal in patients undergoing percutaneous coronary intervention. Methods The study, which was conducted as a prospective randomized controlled study, was carried out with 84 patients: reiki group (n = 28), acupressure group (n = 28), and control group (n = 28). Twenty minutes before the femoral catheter was extracted, 18 minutes of reiki was applied to the seven chakra regions in the reiki group, and 20 minutes of acupressure was applied to the LI4, HT7, and PC6 points in the acupressure group. The control group received standard care. All three groups were given the assessment with Visual Analog Scale, Spielberger State Anxiety Scale, and 5 minutes before & 5 minutes after sheath removal and vital sign data also collected at these time points. Results After the intervention, it was determined that the pain and anxiety scores of both the reiki and acupressure groups were significantly lower than the pain and anxiety scores of the control group (p < 0.05). In addition, heart rate and respiratory rates were significantly lower than the control groups in the measurements made after the intervention of both reiki and acupressure groups (p < 0.05). Systolic and diastolic blood pressures after acupressure, but not after reiki, were significantly lower compared to the control group. Conclusions According to the results of the study, reiki and acupressure applied before the removal of the femoral sheath after percutaneous coronary intervention reduce pain and anxiety and improve vital signs to some extent.