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The purpose of this investigation was to evaluate and compare four oral lubricants in relation to oral mucosal status, perceived relief of dry mouth symptoms, and patient acceptance. Three commercial oral lubricants—two sprays and one gel—and a home remedy of margarine were evaluated. Twenty-five xerostomic/salivary gland dysfunctional patients demonstrating < 0.20 mL/min of unstimulated whole saliva participated in the randomized, four-phase, cross-over study. Each phase included a ten-day use of oral lubricants, followed by a four-day washout period. On the first and tenth days of use, lip and buccal mucosa dryness and perceived oral dryness were evaluated. Patient acceptance of the oral lubricant was evaluated at the end of each ten-day period. The Wilcoxon matched-pairs signed-rank test was used to analyze data over time and between-group differences. The gel group reported a statistically significant improvement in perceived oral dryness from Day 1 to Day 10. No other significant with-in-group differences were found. Subjects rated the gel significantly better than margarine for convenience, perceived value, minutes of relief, and in the “overall” rating. No other significant between-group differences were noted.