Introduction: Chronic diarrhea is characterized by loose stools persisting for over four weeks, affecting approximately 5% of the population, with various infectious and non-infectious causes. It has always posed a diagnostic challenge for gastroenterologists over the years, largely because of the myriads of conditions that present with it.

Objectives: The study explored the endoscopic features and histological findings of patients with chronic watery diarrhea to better understand the etiological factors in Nigeria.

Methodology: A prospective cohort study was conducted at a tertiary healthcare facility, involving patients aged 18 and above with chronic watery diarrhea who had colonoscopy and mucosal biopsy with histology done between 2018 to 2023. The study included 46 patients over the study period.

Results: Most patients (76.1%) had normal colonoscopic findings, while 91.3% exhibited no features of mucosal inflammation. Microscopic colitis was the most common histological diagnosis affecting 76.1% of patients, with lymphocytic colitis being the predominant subtype. Sigmoid colonic tumors and ulcerative colitis were found in a few of the cases.

Conclusion: The high prevalence of microscopic colitis suggests it should be a primary consideration in the differential diagnosis of chronic diarrhea in Nigeria, highlighting the importance of thorough diagnostic evaluations.