ImportanceContrast-associated acute kidney injury (AKI) is a common complication of coronary angiography and percutaneous coronary intervention (PCI) that has been associated with high costs and adverse long-term outcomes.ObjectiveTo determine whether a multifaceted intervention is effective for the prevention of AKI after coronary angiography or PCI.Design, Setting, and ParticipantsA stepped-wedge, cluster randomized clinical trial was conducted in Alberta, Canada, that included all invasive cardiologists at 3 cardiac catheterization laboratories who were randomized to various start dates for the intervention between January 2018 and September 2019. Eligible patients were aged 18 years or older who underwent nonemergency coronary angiography, PCI, or both; who were not undergoing dialysis; and who had a predicted AKI risk of greater than 5%. Thirty-four physicians performed 7820 procedures among 7106 patients who met the inclusion criteria. Participant follow-up ended in November 2020.InterventionsDuring the intervention period, cardiologists received educational outreach, computerized clinical decision support on contrast volume and hemodynamic-guided intravenous fluid targets, and audit and feedback. During the control (preintervention) period, cardiologists provided usual care and did not receive the intervention.Main Outcomes and MeasuresThe primary outcome was AKI. There were 12 secondary outcomes, including contrast volume, intravenous fluid administration, and major adverse cardiovascular and kidney events. The analyses were conducted using time-adjusted models.ResultsOf the 34 participating cardiologists who were divided into 8 clusters by practice group and center, the intervention group included 31 who performed 4327 procedures among 4032 patients (mean age, 70.3 [SD, 10.7] years; 1384 were women [32.0%]) and the control group included 34 who performed 3493 procedures among 3251 patients (mean age, 70.2 [SD, 10.8] years; 1151 were women [33.0%]). The incidence of AKI was 7.2% (310 events after 4327 procedures) during the intervention period and 8.6% (299 events after 3493 procedures) during the control period (between-group difference, −2.3% [95% CI, −0.6% to −4.1%]; odds ratio [OR], 0.72 [95% CI, 0.56 to 0.93]; P = .01). Of 12 prespecified secondary outcomes, 8 showed no significant difference. The proportion of procedures in which excessive contrast volumes were used was reduced to 38.1% during the intervention period from 51.7% during the control period (between-group difference, −12.0% [95% CI, −14.4% to −9.4%]; OR, 0.77 [95% CI, 0.65 to 0.90]; P = .002). The proportion of procedures in eligible patients in whom insufficient intravenous fluid was given was reduced to 60.8% during the intervention period from 75.1% during the control period (between-group difference, −15.8% [95% CI, −19.7% to −12.0%]; OR, 0.68 [95% CI, 0.53 to 0.87]; P = .002). There were no significant between-group differences in major adverse cardiovascular events or major adverse kidney events.Conclusions and RelevanceAmong cardiologists randomized to an intervention including clinical decision support with audit and feedback, patients undergoing coronary procedures during the intervention period were less likely to develop AKI compared with those treated during the control period, with a time-adjusted absolute risk reduction of 2.3%. Whether this intervention would show efficacy outside this study setting requires further investigation.Trial RegistrationClinicalTrials.gov Identifier: NCT03453996