There is a long-standing stigma associated with the use of epinephrine in digital nerve blocks (DNBs) over the concern of digital necrosis. We conducted a systematic review to assess the duration of anesthesia, onset of anesthesia, and complications of lidocaine with epinephrine compared with plain lidocaine for DNBs in adults. We searched Medline via Ovid, Cochrane Library, and ClinicalTrials.gov on January 28, 2020. We included randomized controlled trials that examined lidocaine with epinephrine 1:80,000 to 1:1,000,000 (1-12.5 µg/mL) and plain lidocaine for DNBs of fingers or toes in adults. We completed a blinded review of all unique articles, followed by full-text reviews, data extraction, and quality assessment of all eligible trials. Risk of bias was assessed to inform qualitative data analysis. We identified seven studies with a combined 363 adults and 442 DNBs that met the inclusion criteria. All five studies that reported duration of anesthesia established longer duration in the epinephrine-supplemented lidocaine group, with significant increases in three. Two of the three studies that reported the onset of anesthesia demonstrated significant differences. The two studies that reported complications did not have a single case of digital necrosis. In adults, the use of lidocaine with epinephrine 1:80,000 to 1:1,000,000 (1-12.5 µg/mL) for DNB yields a longer duration of anesthetic effect and seems to be as safe as plain lidocaine in healthy adults. Several studies had some concern for bias, and additional studies are warranted.