Abstract Background: Mailed fecal immunochemical test (FIT) outreach can improve colorectal cancer screening rates, yet little is known about how to optimize these programs for effectiveness and cost. Methods: PROMPT was a pragmatic, stepped-wedge, cluster-randomized effectiveness trial of mailed FIT outreach. Participants in the standard condition were mailed a FIT and received live telephone reminders to return it. Participants in the enhanced condition also received a tailored advance notification (text message or live phone call) and two automated phone call reminders. The primary outcome was 6-month FIT completion; secondary outcomes were any colorectal cancer screening completion at 6 months, implementation, and program costs. Results: The study included 27,585 participants (80% ages 50–64, 82% Hispanic/Latino; 68% preferred Spanish). A higher proportion of enhanced participants completed FIT at 6 months than standard participants, both in intention-to-treat [+2.8%, 95% confidence interval (CI; 0.4–5.2)] and per-protocol [limited to individuals who were reached; +16.9%, 95% CI (12.3–20.3)] analyses. Text messages and automated calls were successfully delivered to 91% to 100% of participants. The per-patient cost for standard mailed FIT was $10.84. The enhanced program's text message plus automated call reminder cost an additional $0.66; live phone calls plus an automated call reminder cost an additional $10.82 per patient. Conclusions: Adding advance notifications and automated calls to a standard mailed FIT program boosted 6-month FIT completion rates at a small additional per-patient cost. Impact: Enhancements to mailed FIT outreach can improve colorectal cancer screening participation. Future research might test the addition of educational video messaging for screening-naïve adults.