Although mode-dependent differences in mortality are for the moment unproven, establishing a health-related quality of life difference between assigned pacing modes would be useful. Such a difference, if one exists, should be >or=0.5 standard deviation units among scales using validated instruments to have significant clinical meaning. Two large data sets, the Canadian Trial of Physiological Pacing (CTOPP) and the Mode Selection Trial (MOST) both similar in design, largely failed to clearly establish such a significant difference. Another trial the Pacemaker Selection in the Elderly (PASE) did suggest that for sinus node disease, DDD-R pacing may lead to an improvement in quality of life mainly early post implant. Two other large trials, UK-PACE and DANPACE have yet to present quality of life related results. All published data have established that restoration of chronotropic competence by pacing leads to improvements in quality of life that are significant. In CTOPP an attempt to quantify a mode-dependent difference for a pacemaker syndrome suggested that the prevalence and clinical importance of pacemaker syndrome may be exaggerated. The relative ease of crossover from VVI-R to DDD, by device upgrade in CTOPP or by programming in MOST, may explain the 2.9% vs. 31% crossover rates seen in CTOPP vs. MOST respectively. Trials to date may have had a mode dependent difference undermined by possible adverse effects from right ventricular apical sites of pacing. Future trial data; DANPACE, sinus node disease AAI-R vs. DDD-R and PAVE, post AVJ ablation VVI-R vs. VVI-CRT, will asses in more detail the role of site of pacing as a factor in determining mode dependent outcomes in pacing.