Could you clarify what you mean by this question? Do you mean, what groups successfully resisted the Spanish before Smallpox? Or do you mean this as a hypothetical "if there was no smallpox could the natives have resisted?"

"Strong enough" might also be missing the point, since military might wasn't the major reason they were conquered. It might be better to think of the Spanish conquests as a series of coups d'etat rather than direct military engagements. Most of the fighting was between native factions, with the Spanish allying themselves with one group or another. The smallpox outbreaks also occurred relatively quickly in the history of the conquest, so there wasn't much time to fight against the Spanish before the outbreaks hit.

There were several groups that held out against the Spanish for a long time, even after the introduction of Smallpox. The Maya of the Yucatan and especially the southern Lowlands resisted for many decades. In the case of Noj Peten, the last Mesoamerican city-state to be conquered, it remained independent until 1697 - almost 2 centuries after the Spanish arrived. If you're interested in reading more about that, I'd recommend The Conquest of the Last Maya Kingdom by Grant D. Jones.