the main conflict of the entire novel
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I think that the main conflict can be found in the main theme of the story. It is the challange of creating civilization in the wild. If, as Cather famouly claimed, the land is the hero of O Pioneers!, then the novel is fundamentally a story of the wilds becoming a civilization. Each of the characters in the story attempt to make the land livable for his or herself, and each character can be judged based on his or her ability to work with the land rather than against it. Please check out this excerpt from the GradeSaver Site. There is greater detail there as well.