BACKGROUND: This randomized, controlled trial assessed the impact of a tailored navigation intervention versus a standard mailed intervention on colorectal cancer screening adherence and screening decision stage (SDS). METHODS: Primary care patients (n = 945) were surveyed and randomized to a Tailored Navigation Intervention (TNI) Group (n = 312), Standard Intervention (SI) Group (n = 316), or usual care CONTROL GROUP (n = 317). TNI Group participants were sent colonoscopy instructions and/or stool blood tests according to reported test preference, and received a navigation call. The SI Group was sent both colonoscopy instructions and stool blood tests. Multivariable analyses assessed intervention impact on adherence and change in SDS at 6 months. RESULTS: The primary outcome, screening adherence (TNI Group: 38%, SI Group: 33%, CONTROL GROUP: 12%), was higher for intervention recipients than controls (P = 0.001 and P = 0.001, respectively), but the two intervention groups did not differ significantly (P = 0.201). Positive SDS change (TNI Group: +45%, SI Group: +37%, and CONTROL GROUP: +23%) was significantly greater among intervention recipients than controls (P = 0.001 and P = 0.001, respectively), and the intervention group difference approached significance (P = 0.053). Secondary analyses indicate that tailored navigation boosted preferred test use, and suggest that intervention impact on adherence and SDS was attenuated by limited access to screening options. CONCLUSIONS: Both interventions had significant, positive effects on outcomes compared with usual care. TNI versus SI impact had a modest positive impact on adherence and a pronounced effect on SDS. IMPACT: Mailed screening tests can boost adherence. Research is needed to determine how preference, access, and navigation affect screening outcomes.