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Background Colonoscopy is the most widely used colorectal cancer (CRC) screening test in the United States. Through the detection and removal of potentially precancerous polyps, it can prevent CRC. However, CRC screening remains low among adults who are recommended for screening. The New Hampshire Colorectal Cancer Screening Program implemented a patient navigation (PN) intervention to increase colonoscopy screening among low‐income patients in health centers in New Hampshire. In the current study, the authors examined the cost‐effectiveness of this intervention. Methods A decision tree model was constructed using Markov state transitions to calculate the costs and effectiveness associated with PN. Costs were calculated for the implementation of PN in a statewide public health program and in endoscopy centers. The main study outcome was colonoscopy screening completion. The main decision variable was the incremental cost‐effectiveness ratio associated with the PN intervention compared with usual care. Results The average cost per screening with PN was $1089 (95% confidence interval, $1075‐$1103) compared with $894 with usual care (95% confidence interval, $886‐$908). Among patients who were navigated, approximately 96.2% completed colonoscopy screening compared with 69.3% of those receiving usual care (odds ratio, 11.2; P <. 001). The incremental cost‐effectiveness ratio indicated that 1 additional screening completion cost approximately $725 in a public health program and $548 in an endoscopy center with PN compared with usual care, both of which are less than the average Medicare reimbursement of $737 for a colonoscopy procedure. Conclusions PN was found to be cost‐effective in increasing colonoscopy screening among low‐income adults in the New Hampshire Colorectal Cancer Screening Program, even at the threshold of current Medicare reimbursement rates for colonoscopy. The results of the current study support the implementation of PN in statewide public health programs and endoscopy centers.