ABSTRACT. The aim was to observe the relationship of pacemaker programming and patients' outcome in an unselected population of recipients in real-world practice. Pacemaker programming at hospital discharge and at scheduled follow-up visits was recorded and classified as physiologic based on simple principles: avoidance of unnecessary ventricular stimulation in patients without atrioventricular block, avoidance of unnecessary atrial stimulation in those without sinus node dysfunction, rate increase in those with chronotropic incompetence, and avoidance of hypotension-related symptoms. All-cause 2-year mortality was the primary endpoint; atrial fibrillation (AF) episodes leading to unplanned visits/hospitalizations was the secondary endpoint. A total of 1740 patients were followed for 24 ± 3 months, 89% had DDD(R) pacemakers; physiologic programming was not associated with better survival, but it was associated with a lower incidence of AF episodes in the 810 patients with AV block as primary pacemaker indication (6.5% versus 11%, po0.01). Physiologic pacemaker programming occurred in only 41.4% of patients at hospital discharge; reprogramming towards a physiologic setting occurred in 8.7% at follow-up, mainly (76%) within the first 6 months. Physiologic programming is associated with a lower incidence of AF episodes in AV block patients beyond maintenance of AV synchrony. Proactive pacemaker behavior to increase physiologic programming should be considered, in view of physicians' reluctance to change programming from shipment settings.