Objective The purpose of this study was to explore system and clinician‐related barriers, and predictors for the adoption of the National Comprehensive Cancer Network Distress Management Guideline (DMG) into oncology outpatient practice. Methods This descriptive, correlational study surveyed a national sample of oncology nurses working in an outpatient setting who completed the survey electronically or by mail. Results Study respondents (n = 409) were predominantly certified nurses (84%) yet largely unfamiliar with the DMG; 17% of respondents were using the DMG. Time, staff uncertainties and ambiguous accountability were the largest barriers to not assessing distress. Compared with those not using any assessment tool, those using the DMG were more comfortable discussing distress, worked as an oncology nurse longer, scored colleagues higher on valuing distress screening and had more organizational processes in place to support evidence‐based practices. Significant predictors of DMG use included higher familiarity with the DMG (OR 3.81, p < .001), lower perceived barriers (OR 0.41, p = .001), non‐profit status (OR 3.93, p = .05) and urban or rural (versus suburban) work settings (OR 04.59, p = .04; overall model chi‐square 133.25, df 12, p < .001, Nagelkerke R2 .67). Conclusions This study identified barriers and predictors to using the DMG, which are amenable to interventions. DMG adoption may be augmented by interventions, which increase familiarity with the guideline. Additionally, adoption of the DMG may improve through explicit articulation of the responsibilities oncology team members have in cancer‐related distress screening and management. Further studies are needed to evaluate the efficacy of such interventions and their impact on patient care outcomes. Copyright © 2013 John Wiley & Sons, Ltd.