We evaluate the sensitivity and specificity of point-of-care ultrasonography, performed by ultrasonographic fellowship-trained emergency physicians and physician assistants, compared with computed tomography (CT) scan in diagnosing acute diverticulitis in the emergency department (ED). This was a prospective observational study of a convenience sample of patients with suspected diverticulitis who were treated at an academic ED between 2017 and 2020. Sonographers were blinded to clinical data, laboratory results, and CT scan findings. A total of 19 ultrasonographic fellowship-trained emergency physicians and physician assistants performed the ultrasonographic examinations. Point-of-care ultrasonographic diagnosis of acute diverticulitis was defined as the presence of bowel wall thickening, greater than 5 mm, surrounding a diverticulum, enhancement of the surrounding pericolonic fat, and sonographic tenderness to palpation. The primary outcome measures were sensitivity, specificity, positive predictive value, and negative predictive value of point-of-care ultrasonography in the diagnosis of diverticulitis compared with CT, which was considered the criterion standard. Data from 452 patients were analyzed. Median age was 60 years, 54% were women, and 36% had a diagnosis of diverticulitis based on CT scan. Of the 452 patients, there were 13 false-positive (3%) and 10 false-negative (2%) point-of-care ultrasonographic examinations. Overall, compared with CT, point-of-care ultrasonography had a sensitivity of 92% (95% confidence interval 88% to 96%), specificity of 97% (95% confidence interval 94% to 99%), positive predictive value of 94% (95% confidence interval 90% to 97%), and negative predictive value of 96% (93% to 98%) in the diagnosis of diverticulitis. In a convenience sample of ED patients with suspected diverticulitis, point-of-care ultrasonography performed by ultrasonographic fellowship-trained emergency physicians and physician assistants could be used as an imaging modality for diagnosing acute diverticulitis, with high sensitivity and specificity compared with CT scan.