This study aimed to assess the relative importance of demographic, interpersonal, and personality factors in predicting sexual infidelity in heterosexual couples. A total of 506 men (M age = 32.86 years, SD = 10.60) and 412 women (M age = 27.66 years, SD = 8.93), who indicated they were in a monogamous sexual relationship, completed a series of questionnaires, including the Sexual Excitation/Inhibition (SES/SIS) scales and the Mood and Sexuality Questionnaire, and answered questions about, among others, religiosity, education, income, relationship and sexual satisfaction, and sexual compatibility. Almost one-quarter of men (23.2%) and 19.2% of women indicated that they had "cheated" during their current relationship (i.e., engaged in sexual interactions with someone other than their partner that could jeopardize, or hurt, their relationship). Among men, a logistic regression analysis, explaining 17% of the variance, revealed that a higher propensity of sexual excitation (SES) and sexual inhibition due to "the threat of performance concerns" (SIS1), a lower propensity for sexual inhibition due to "the threat of performance consequences" (SIS2), and an increased tendency to engage in regretful sexual behavior during negative affective states were all significant predictors of infidelity. In women, a similar regression analysis explained 21% of the variance in engaging in infidelity. In addition to SIS1 and SIS2, for which the same patterns were found as for men, low relationship happiness and low compatibility in terms of sexual attitudes and values were predictive of infidelity. The findings of this study suggest that, for both men and women, sexual personality characteristics and, for women, relationship factors are more relevant to the prediction of sexual infidelity than demographic variables such as marital status and religiosity.