Background and Aims <p>Antibodies targeting bacterial cytolethal distending toxin subunit B (CdtB) and vinculin are diagnostic of post-infection irritable bowel syndrome (IBS). In this study, we explored the temporal behavior of anti-CdtB and anti-vinculin antibodies and potential relationships to IBS symptoms. The potential impacts of antibody reduction therapies were also assessed.</p> Methods <p>A retrospective chart review of 417 IBS patients who had been tested for anti-CdtB and anti-vinculin antibodies was performed. Anti-vinculin and anti-CdtB antibody levels, time to normalization of antibody levels, and IBS symptoms’ burdens and changes were assessed. Use of antibody-depleting therapies (intravenous immunoglobulin [IVIG] or plasmapheresis exchange [PLEX]) vs. usual management was also recorded.</p> Results <p>158 subjects (38.5%) were positive for either anti-CdtB or anti-vinculin. In subjects with multiple tests (total <i>N</i> = 38), normalization of anti-vinculin levels over time correlated with improvements in IBS symptoms (<i>p</i> = 0.020). Plasmapheresis (PLEX) or intravenous immunoglobulins (IVIG) treatments were associated with greater antibody normalization than usual management (<i>p</i> = 0.046).</p> Conclusions <p>Anti-CdtB and anti-vinculin antibodies are common in post-infection IBS, and anti-vinculin levels may correlate with severity of IBS symptoms.</p>