As we increasingly integrate technology into our lives, we need a better framework for understanding social interactions across the communication landscape. Utilizing survey data in which more than 4,600 people across the United States, India, and Japan described a recent social interaction, this article qualitatively and quantitatively explores what makes an interaction meaningful. A qualitative analysis of respondents’ own words finds that meaningful interactions are those with emotional, informational, or tangible impact that people believe enhance their lives, the lives of their interaction partners, or their personal relationships. A quantitative analysis predicting respondents’ ratings of recent interactions finds the attributes most likely to facilitate meaningfulness include strong ties (e.g., friends and family), community ties (e.g., neighbors), shared activities, and synchronicity; meaningful social interactions are also more likely to be planned in advance and memorialized with photos or videos. These attributes are consistent across cultures. Although popular rhetoric often juxtaposes people’s online lives against their offline lives, this research finds in-person interactions can be just as meaningful as technology-mediated interactions. We conclude with a new framework for thinking about social interactions more holistically.