Surgical site infection is low following endoscopic carpal tunnel release (ECTR), yet antibiotic prophylaxis is still common in these procedures. This study piloted a randomized, double-blind, placebo-controlled study design at a community hospital to generate discourse in support of discontinuing antibiotic prophylaxis in ECTR procedures. Patients undergoing dual-incision endoscopic carpal tunnel release at a single community hospital between May 1, 2018 and December 31, 2020 were enrolled in a pilot study. Subjects were randomized to prophylactic antibiotics or placebo saline solution arms. Infection rates and complications were compared. Study workflow processes were streamlined to facilitate eventual study duplication at additional sites. One hundred twenty-four subjects (140 hands) were included in the final analysis. No subjects in either study arm sustained an infection. The race and ethnic distributions of the study sample closely resembled those of the census-reported community distributions. Implementing a randomized, double-blind, placebo-controlled study at a community hospital presented numerous challenges. Although statistical nor clinical significance could be established in the absence of infection, these results validate what is presently known regarding the low likelihood of infection in clean hand surgery and demonstrated the feasibility of designing and implementing methodologically sound research in a community setting. Duplicating this study design at additional research sites can provide the level of evidence necessary to discourage unnecessary prophylactic antibiotic administration in clean hand surgery. • Surgical site infection following endoscopic carpal tunnel release is very low. • Prophylactic antibiotics may not be necessary in carpal tunnel procedures. • A randomized-controlled trial was successfully piloted at a community hospital. • This study design can be duplicated at more sites to obtain higher power.