Resumen: Background:Social media is now a common context wherein people express their feelings in real time. These platforms are increasingly showing their potential to detect the mental health status of the population. Suicide prevention is a global health priority and efforts toward early detection are starting to develop, although there is a need for more robust research. Objective:We aimed to explore the emotional content of Twitter posts in Spanish and their relationships with severity of the risk of suicide at the time of writing the tweet. Methods:Tweets containing a specific lexicon relating to suicide were filtered through Twitter's public application programming interface. Expert psychologists were trained to independently evaluate these tweets. Each tweet was evaluated by 3 experts. Tweets were filtered by experts according to their relevance to the risk of suicide. In the tweets, the experts evaluated: (1) the severity of the general risk of suicide and the risk of suicide at the time of writing the tweet (2) the emotional valence and intensity of 5 basic emotions; (3) relevant personality traits; and (4) other relevant risk variables such as helplessness, desire to escape, perceived social support, and intensity of suicidal ideation. Correlation and multivariate analyses were performed. Results:Of 2509 tweets, 8.61% (n=216) were considered to indicate suicidality by most experts. Severity of the risk of suicide at the time was correlated with sadness (ρ=0.266; P<.001), joy (ρ=–0.234; P=.001), general risk (ρ=0.908; P<.001), and intensity of suicidal ideation (ρ=0.766; P<.001). The severity of risk at the time of the tweet was significantly higher in people who expressed feelings of defeat and rejection (P=.003), a desire to escape (P<.001), a lack of social support (P=.03), helplessness (P=.001), and daily recurrent thoughts (P=.007). In the multivariate analysis, the intensity of suicide ideation was a predictor for the severity of suicidal risk at the time (β=0.311; P=.001), as well as being a predictor for fear (β=–0.009; P=.01) and emotional valence (β=0.007; P=.009). The model explained 75% of the variance. Conclusions:These findings suggest that it is possible to identify emotional content and other risk factors in suicidal tweets with a Spanish sample. Emotional analysis and, in particular, the detection of emotional variations may be key for real-time suicide prevention through social media. Idioma: Inglés DOI: 10.2196/31800 Año: 2022 Publicado en: JMIR public health and surveillance 8, 5 (2022), e31800 ISSN: 2369-2960 Factor impacto JCR: 8.5 (2022) Categ. JCR: PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH rank: 8 / 180 = 0.044 (2022) - Q1 - T1 Categ. JCR: PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH rank: 15 / 207 = 0.072 (2022) - Q1 - T1 Factor impacto CITESCORE: 12.3 - Medicine (Q1)