Previous research finds cultural differences in response to activities designed to increase happiness, or Positive Psychological Intervention (PPIs). The goal of the present study is to explore why different cultural groups respond differently to PPIs. Specifically, we examined responsiveness to PPIs in three cultural groups—Anglo-American, Asian American, and Indian (living in India)—both quantitatively and qualitatively. Participants (n = 469) were recruited and participated in the study via Amazon Mechanical Turk and were randomly assigned to a 15-min writing task focused on gratitude, optimism, or daily activities (control). As expected, we observed a culture by condition interaction whereby Anglo-Americans experienced increases in positive emotion with both gratitude and optimism tasks, but Indian participants experienced increases in both positive emotion and negative emotion when practicing gratitude, but not optimism. Qualitative analyses revealed possible causes for variability in success of PPIs in different cultures, and suggest possible adjustments that could be made to improve their efficacy. In summary, we observed differences in response to gratitude, but not optimism, which may be fueled by an adverse affective response among non-Anglo-American participants—Gratitude makes them feel good, but also sad and guilty.