BACKGROUND: Increasing the use of electronic medical records (EMR) has been suggested as an important strategy for improving healthcare safety. OBJECTIVE: To sequentially measure, evaluate, and respond to safety culture and practice safety concerns following EMR implementation. DESIGN: Safety culture was assessed using a validated tool (Safety Attitudes Questionnaire; SAQ), immediately following EMR implementation (T1) and at 1.5 (T2) and 2.5 (T3) years post-implementation. The SAQ was supplemented with a practice-specific assessment tool to identify safety needs and barriers. PARTICIPANTS: A large medical group practice with a primary care core of 17-18 practices, staffed by clinicians in family medicine, pediatrics, internal medicine. INTERVENTIONS: Survey results were used to define and respond to areas of need between assessments with system changes and educational programs. MAIN MEASURES: Change in safety culture over time; perceived impact of EMR on practice. KEY RESULTS: Responses were received from 103 of 123 primary care providers in T1 (83.7 % response rate), 122 of 143 in T2 (85.3 %) and 142 of 181 in T3 (78.5 %). Safety culture improved over this period, with statistically significant improvement in all domains except for stress recognition. Time constraints, communications and patient adherence were perceived to be the most important safety issues. The majority of respondents in both T2 (77.9 %) and T3 (85.4 %) surveys agreed that the EMR improved their ability to provide care more safely. CONCLUSIONS: Implementation of an EMR in a large primary care practice required redesign of many organizational processes, and was associated with improvements in safety culture. Most primary care providers agreed that the EMR allowed them to provide care more safely.