Atrial fibrillation (AF) is characterized by short and irregular ventricular cycle lengths (VCL). While the beneficial effects of heart rate slowing (i.e., the prolongation of VCL) in AF are well recognized, little is known about the impact of irregularity. In 10 anesthetized dogs, R-R intervals, left ventricular (LV) pressure, and aortic flow were collected for >500 beats during fast AF and when the average VCL was prolonged to 75%, 100%, and 125% of the intrinsic sinus cycle length by selective atrioventricular (AV) nodal vagal stimulation. We used the ratio of the preceding and prepreceding R-R intervals (RR(p)/RR(pp)) as an index of cycle length irregularity and assessed its effects on the maximum LV power, the minimum of the first derivative of LV pressure, and the time constant of relaxation by using nonlinear fitting with monoexponential functions. During prolongation of VCL, there was a pronounced decrease in curvature with the formation of a plateau, indicating a lesser dependence on RR(p)/RR(pp). We conclude that prolongation of the VCL during AF reduces the sensitivity of the LV performance parameters to irregularity.