Aim. To provide insight into the impact of substituting general practitioners with nurse practitioners in out-of-hours services on: (1) the number of patients; and (2) general practitioners' caseload (patient characteristics, urgency levels, types of complaints). Background. General practitioners' workload during out-of-hours care is high, and the number of hours they work out-of-hours has increased, which raises concerns about maintaining quality of care. One response to these challenges is shifting care to nurse practitioners. Design. Quasi-experimental study comparing differences between and within outof-hours teams: experimental, one nurse practitioner and four general practitioners; control, five general practitioners. Methods. Data of 12,092 patients from one general practitioners cooperative were extracted from medical records between April 2011 and July 2012. Results. The number of patients was similar in the two study arms. In the experimental arm, the nurse practitioner saw on average 16Á3% of the patients and each general practitioner on average 20Á9% of the patients. General practitioners treated more older patients; higher urgency levels; and digestive, cardiovascular and neurological complaints. Nurse practitioners treated more patients with skin and respiratory complaints. Substitution did not lead to a meaningful increase of general practitioners' caseload. Conclusion. The results show that nurse practitioners can make a valuable contribution to patient care during out-of-hours. The patients managed and care provided by them is roughly the same as general practitioners. In areas with a shortage of general practitioners, administrators could consider employing nurses who are competent to independently treat patients with a broad range of complaints to offer timely care to patients with acute problems.