BACKGROUND.Colorectal cancer screening is underutilized. The objective of the current study was to determine whether targeted and tailored interventions can increase screening use.METHODS.A total of 1546 primary care practice patients completed a baseline telephone survey and were randomized to 4 study groups: control (387 patients), Standard Intervention (SI) (387 patients), Tailored Intervention (TI) (386 patients), or Tailored Intervention plus Phone (TIP) (386 patients). The control group received usual care throughout the study. The SI group received a targeted intervention by mail (ie, screening invitation letter, informational booklet, stool blood test, and reminder letter). The TI group received the targeted intervention with tailored “message pages.” The TIP group received the targeted intervention, tailored message pages, and a telephone reminder. Intervention group contacts were repeated 1 year later. Screening was assessed 24 months after randomization.RESULTS.Screening rates in study groups were 33% in the control group, 46% in the SI group, 44% in the TI group, and 48% in the TIP group. Screening was found to be significantly higher in all 3 intervention groups compared with the control group (odds ratio [OR] of 1.7 [95% confidence interval (95% CI), 1.3–2.5], OR of 1.6 [95% CI, 1.2–2.1], and OR of 1.9 [95% CI, 1.4–2.6], respectively), but did not vary significantly across intervention groups. Multivariate analyses demonstrated that older age, education, past cancer screening, screening preference, response efficacy, social support and influence, and exposure to study interventions were positive predictors of screening. Having worries and concerns about screening was found to be a significant negative predictor.CONCLUSIONS.Targeted and tailored interventions were found to increase colorectal cancer screening use. However, additional research is needed to determine how to increase the effect of such interventions in primary care. Cancer 2007. © 2007 American Cancer Society.