Prior research found that user personality significantly affects technology acceptance perceptions and decisions. Yet, evidence on the moderating influence of user gender on the relationship between personality and technology acceptance is barely existent despite theoretical consideration. Considering this research gap, the present study reports the results of a survey in which we examined the relationships between personality and technology acceptance from a gender perspective. This study draws upon a sample of N = 686 participants (n = 209 men, n = 477 women) and applied the HEXACO Personality Inventory—Revised along with established technology acceptance measures. The major result of this study is that we do not find significant influence of user gender on the relationship between personality and technology acceptance, except for one aspect of personality, namely altruism. We found a negative association between altruism and intention to use the smartphone in men, but a positive association in women. Consistent with this finding, we also found the same association pattern for altruism and predicted usage: a negative one in men and a positive one in women. Implications for research and practice are discussed, along with limitations of the present study and possible avenues for future research.