Religious and spiritual struggles arise in various forms and circumstances. The newly developed Religious and Spiritual Struggles (RSS) scale reveals a coherent, multidimensional structure in these domain-specific problems that applies to religious and nonreligious people alike. Thus new questions emerge. Do religious people struggle less with religion, or more? Struggles and stress seem likely to coincide, but might stressful life events give rise to fewer religious struggles among religious people? We tested this moderation hypothesis in a large sample of American undergraduates, who completed the RSS and measures of stressful life events, religious belief salience, and religious participation. Latent interaction factors for religiousness and stressful life events failed to predict additional variance in most RSS factors in a structural equation model using polychoric correlations, yielding no support for the moderation hypothesis. However, religiousness and stressful life events independently predicted higher scores on most factors of the RSS in most samples.