Bi2Sr2CaCu2Ox (Bi-2212) superconducting wires are of interest for producing the next generation of high field (greater than 20 T) magnet windings. However, improvements in critical current must be achieved to make them fully viable for such applications. Fully optimizing the thermal reaction in the melt-processing is a means of maximizing the capabilities of wires presently available. Using methods of Statistically Designed Experiments, the process variables may be simultaneously optimized to maximize c, and in this work, we show the effects of including and varying the parameters of a pre-anneal in the thermal reaction cycle. We find that the critical current is less sensitive to changes in the pre-anneal temperature, and is more responsive to changes in the dwell time. We examine the microstructure for varied dwell times and show the fitted response surfaces for c as a function of the pre-anneal parameters.