IMPORTANCEColorectal cancer screening rates are suboptimal, particularly among sociodemographically disadvantaged groups.OBJECTIVETo examine whether guaranteed money or probabilistic lottery financial incentives conditional on completion of colorectal cancer screening increase screening uptake, particularly among groups with lower screening rates.DESIGN, SETTING, AND PARTICIPANTSThis parallel, 3-arm randomized clinical trial was conducted from March 13, 2017, through April 12, 2018, at 21 medical centers in an integrated health care system in western Washington. A total of 838 age-eligible patients overdue for colorectal cancer screening who completed a questionnaire that confirmed eligibility and included sociodemographic and psychosocial questions were enrolled.INTERVENTIONSInterventions were (1) mail only (n = 284; up to 3 mailings that included information on the importance of colorectal cancer screening and screening test choices, a fecal immunochemical test [FIT], and a reminder letter if necessary), (2) mail and monetary (n = 270; mailings plus guaranteed $10 on screening completion), or (3) mail and lottery (n = 284; mailings plus a 1 in 10 chance of receiving $50 on screening completion).MAIN OUTCOMES AND MEASURESThe primary outcome was completion of any colorectal cancer screening within 6 months of randomization. Secondary outcomes were FIT or colonoscopy completion within 6 months of randomization. Intervention effects were compared across sociodemographic subgroups and self-reported psychosocial measures.RESULTSA total of 838 participants (mean [SD] age, 59.7 [7.2] years; 546 [65.2%] female; 433 [52.2%] white race and 101 [12.1%] Hispanic ethnicity) were included in the study. Completion of any colorectal screening was not significantly higher for the mail and monetary group (207 of 270 [76.7%]) or the mail and lottery group (212 of 284 [74.6%]) than for the mail only group (203 of 284 [71.5%]) (P = .11). For FIT completion, interventions had a statistically significant effect (P = .04), with a net increase of 7.7% (95% CI, 0.3%–15.1%) in the mail and monetary group and 7.1% (95% CI, −0.2% to 14.3%) in the mail and lottery group compared with the mail only group. For patients with Medicaid insurance, the net increase compared with mail only in FIT completion for the mail and monetary or the mail and lottery group was 37.7% (95% CI, 11.0%–64.3%) (34.2% for the mail and monetary group and 40.4% for the mail and lottery group) compared with a net increase of only 5.6% (95% CI, −0.9% to 12.2%) among those not Medicaid insured (test for interaction P = .03).CONCLUSIONS AND RELEVANCEFinancial incentives increased FIT uptake but not overall colorectal cancer screening. Financial incentives may decrease screening disparities among some sociodemographically disadvantaged groups.TRIAL REGISTRATIONClinicalTrials.gov identifier: