Multitarget stool DNA (mt-sDNA) is an increasingly utilized noninvasive option for colorectal cancer screening; however, its impact is limited by imperfect test adherence. Tailored patient navigation (TPN) improves adherence for other cancer screening tests, but its role in mt-sDNA is not known.

Determine whether TPN improves mt-sDNA completion and reduces sample could not be processed (SCNBP) result rates.

A large, urban, academic primary care clinic serving a medically vulnerable population.

All patients who received mt-sDNA order in 2022 and 2023.

A patient navigator outreached all patients ordered mt-sDNA to support test completion during the 12-month intervention period in 2023.

Rates of mt-sDNA completion within 90 days and SCNBP results were compared between the 12-month intervention and pre-intervention periods using generalized estimating equations. A total of 2694 patients received 3297 orders during the study. TPN was significantly associated with improved rates of 90-day mt-sDNA completion (51% vs. 39%, OR 1.67, p < .001) and SCNBP results (4% vs. 5%, OR 0.55, p < .001).

Tailored patient navigation was associated with improved rates of mt-sDNA completion and SCNBP results despite built-in navigation services provided by the manufacturer. TPN for mt-sDNA is a promising strategy for enhancing colorectal cancer screening uptake.