Hemolysis has been suggested as a feature conferring increased pathogenicity to certain Propionibacterium acnes strains in the setting of shoulder infection. The purpose of this study was to compare the virulence of hemolytic and nonhemolytic P acnes strains in patients undergoing revision shoulder arthroplasty. Thirty-nine patients with at least 1 positive culture growth for P acnes at the time of revision surgery were identified with P acnes isolates available for hemolysis testing. Patients were grouped into those with P acnes isolates positive (n = 20) and negative (n = 19) for hemolysis. The groups were retrospectively compared based on objective perioperative findings around the time of revision surgery and the postoperative clinical course, including the need for revision surgery. All cases were classified into categories of infection (definite infection, probable infection, and probable contaminant) based on objective perioperative criteria. The presence of hemolysis was not significantly associated with an increased likelihood of infection (P = .968). Hemolysis demonstrated a 75% sensitivity and 26% specificity for determining infection (definite infection and probable infection categories). The hemolytic and nonhemolytic groups showed no difference regarding preoperative serum erythrocyte sedimentation rate and/or C-reactive protein level (P = .70), number of positive cultures (P = .395), time to positive culture (P = .302), and presence of positive frozen section findings (P = .501). Postoperatively, clindamycin resistance, shoulder function, and the rate of reoperation were not significantly different between the hemolytic and nonhemolytic groups. The presence of hemolysis was not associated with increased pathogenicity in patients with P acnes-positive cultures following revision shoulder arthroplasty, when assessed by objective perioperative criteria and the postoperative clinical course.