Background <p>Nontraumatic ileal perforation is a cause of obscure peritonitis characterized by severe toxicity and high mortality. This burden is disproportionately greater in LMICs due to poor hygiene practices, burden of HIV infection, and other comorbidities.</p> <p>This study aimed at determining the prevalence, anatomic-pathologic findings, and factors associated with nontraumatic ileal perforation a multicenter cross‑sectional study at 3 selected hospitals in Uganda.</p> Methods <p>This was a cross-sectional study of 149 consecutive sample participants that used a structured checklist. We conducted logistic regression analyses using SPSS v21.0 (IBM), Variables with p &lt; 0.20 in the bivariate analysis were entered into the multivariable logistic regression model, and p &lt; 0.05 was considered statistically significant.</p> Results <p>Nontraumaticileal perforation was more prevalent among males (20.1%; 149) and peasants/farmers (41.6%; 149) of rural residence (22.1%; 149). The majority of the study participants had typhoid perforations (79.1%; 149). Most ileal perforations occurred 20-39 cm from the ileocecal junction (76.4%; 149), a perforation size/diameter of 0.5-1cm was more common (58.1%; 149), and a single isolated perforation was more common (74.4%; 149). However, all perforations mainly occurred at the ante mesenteric border. Being an HIV-positive person was associated with greater odds of developing NTIP than was being a non-HIV-positive person. AOR 8.344, p = 0.015 (p&lt;0.05). Additionally, patients treated with open and closed pit latrines were more likely to develop nontraumatic perforation than were those treated with water flash latrines. AOR 12.971, p = 0.004 (p &lt; 0.05).</p> Conclusion <p>This study established that nontraumaticileal perforation is more prevalent among male peasants living in rural areas and with typhoid fever and most of ileal perforations were due to typhoid fever.</p>