Shoulder pain is a common transient side-effect of vaccination. Infrequently, patients can develop prolonged shoulder pain and dysfunction following vaccination. A series of 13 cases are described in which persistent shoulder dysfunction and pain developed following immunization. Common clinical characteristics included absence of a history of prior shoulder dysfunction, previous exposure to vaccine administered, rapid onset of pain, and limited range of motion. The proposed mechanism of injury is the unintentional injection of antigenic material into synovial tissues resulting in an immune-mediated inflammatory reaction. Careful consideration should be given to appropriate injection technique when administering intramuscular vaccinations to reduce the risk of shoulder injury.