The perfusion index (PI) is an objective tool used to assess a successful nerve block. Epinephrine is a widely used adjuvant to local anesthetics, and it may affect PI values because of the vasoconstrictive property. The aim of this study was to investigate the influence of epinephrine on PI as an indicator of a successful block in ultrasound-guided supraclavicular brachial plexus block (SCBPB). In this randomized controlled trial, 82 adult patients underwent upper limb surgery under SCBPB were recruited between July 2018 and March 2019 in a single tertiary care center. Participants were randomly assigned to one of two groups: non-epinephrine group (n = 41) or epinephrine group (5 mcg ml-1, n = 41). The primary outcome was the comparison of the "PI ratio 10," which was defined as the ratio of the PI 10 to the baseline. Receiver operating characteristic (ROC) curves were constructed to determine the accuracy of the PI in predicting the block success at each time interval. The PI ratio 10 was 2.7 (1.9-4.0) in non-epinephrine group and 3.3 (2.2-4.4) in epinephrine group (median difference: 0.4; 95% confidence interval [CI] - 1.1 to 0.2; P = 0.207). The ROC curves compared without group identification were not significantly different over time. The cut-off value for the PI and PI ratio at 5 min (PI ratio 5) were 7.7 (area under the ROC [AUROC]: 0.89, 95% CI 0.83-0.94) and 1.6 (AUROC: 0.94, 95% CI 0.90-0.98), respectively. The perineural epinephrine did not affect the PI following a SCBPB. The PI ratio 5 > 1.6 might be considered as a relatively accurate predictor of a successful SCBPB.Trial registration: This study was registered at the Clinical Trial Registry of Korea (https://cris.nih.go.kr. CriS No. KCT0003006).