Most evaluations of pay-for-performance (P4P) incentives have focused on large-group practices. Thus, the effect of P4P in small practices, where many US residents receive care, is largely unknown. Furthermore, whether electronic health records (EHRs) with chronic disease management capabilities support small-practice response to P4P has not been studied.To assess the effect of P4P incentives on quality in EHR-enabled small practices in the context of an established quality improvement initiative.A cluster-randomized trial of small (<10 clinicians) primary care clinics in New York City from April 2009 through March 2010. A city program provided all participating clinics with the same EHR software with decision support and patient registry functionalities and quality improvement specialists offering technical assistance.Incentivized clinics were paid for each patient whose care met the performance criteria, but they received higher payments for patients with comorbidities, who had Medicaid insurance, or who were uninsured (maximum payments: $200/patient; $100,000/clinic). Quality reports were given quarterly to both the intervention and control groups.Comparison of differences in performance improvement, from the beginning to the end of the study, between control and intervention clinics for aspirin or antithrombotic prescription, blood pressure control, cholesterol control, and smoking cessation interventions. Mixed-effects logistic regression was used to account for clustering of patients within clinics, with a treatment by time interaction term assessing the statistical significance of the effect of the intervention.Participating clinics (n = 42 for each group) had similar baseline characteristics, with a mean of 4592 (median, 2500) patients at the intervention group clinics and 3042 (median, 2000) at the control group clinics. Intervention clinics had greater adjusted absolute improvement in rates of appropriate antithrombotic prescription (12.0% vs 6.1%, difference: 6.0% [95% CI, 2.2% to 9.7%], P = .001 for interaction term), blood pressure control (no comorbidities: 9.7% vs 4.3%, difference: 5.5% [95% CI, 1.6% to 9.3%], P = .01 for interaction term; with diabetes mellitus: 9.0% vs 1.2%, difference: 7.8% [95% CI, 3.2% to 12.4%], P = .007 for interaction term; with diabetes mellitus or ischemic vascular disease: 9.5% vs 1.7%, difference: 7.8% [95% CI, 3.0% to 12.6%], P = .01 for interaction term), and in smoking cessation interventions (12.4% vs 7.7%, difference: 4.7% [95% CI, -0.3% to 9.6%], P = .02 for interaction term). Intervention clinics performed better on all measures for Medicaid and uninsured patients except cholesterol control, but no differences were statistically significant.Among small EHR-enabled clinics, a P4P incentive program compared with usual care resulted in modest improvements in cardiovascular care processes and outcomes. Because most proposed P4P programs are intended to remain in place more than a year, further research is needed to determine whether this effect increases or decreases over time.clinicaltrials.gov Identifier: NCT00884013.