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BACKGROUND Obstructed defecation syndrome is a common multifactorial disease whose treatment is based primarily on clinic presentation for the lack of reliable instrumental and anatomopathological criteria. OBJECTIVE We analyzed the pathological findings of the resected rectal specimens after stapled transanal rectal resection in patients affected by outlet obstruction. DESIGN This was a retrospective cohort study. SETTINGS The setting was a university hospital. PATIENTS Patients who underwent rectal resection for obstructed defecation syndrome due to internal rectal prolapse. INTERVENTIONS Specimens of obstructed defecation syndrome patients were analyzed through conventional histology and morphometric image analysis and compared to the ones of rectal specimens excised for oncological diseases. MAIN OUTCOME MEASURES The primary outcome was to investigate the anatomopathological impairments underlying rectal prolapse. RESULTS From January 2017 to December 2020, 46 specimens from the stapled transanal rectal resection group were compared with 40 specimens from the control group. At conventional histology in stapled transanal rectal resection group, 34 samples (73.9%) presented a moderate-severe fibrosis grade with a moderate grade of nerve degeneration in 33 cases (71.7%). In the control group, conventional histology revealed fibrosis absence in 31 specimens (77.5%), while the absence of nerve degeneration was detected in 37 controls (92.5%). In the stapled transanal rectal resection group, morphometric image analysis showed moderate fibrosis and severe fibrosis in 19 (41.3%) and 25 (54.4%) cases, respectively. In the control group, morphometric image analysis showed only low grade of fibrosis in 11 cases (27.5%). A significant difference in all fibrosis and nerve dysplasia grades between groups was found in conventional histology and morphometric image analysis evaluations (p < 0.001). LIMITATIONS The small sample size and the retrospective design of the study. Moreover, there is no chance to use as control group specimens from healthy volunteers. CONCLUSIONS Stapled transanal rectal resection specimens showed a higher fibrosis and nerve dysplasia rate, an important parameter that nowadays is preoperatively completely unconsidered and in a near future could address patients with rectal prolapse to the best treatment approach. See Video Abstract at http://links.lww.com/DCR/B928.