Objectives In the Netherlands, there was a sharp increase in the number of suicides among 10- to 19-year-olds in 2017. A multi-method psychological autopsy study (PA) was conducted to assess feasibility, identify related factors, and study the interplay of these factors to inform suicide prevention strategies. Methods Coroners identified youth suicides in 2017 in their records and then general practitioners (GPs) contacted the parents of these youths. Over a period of 7 months, 66 qualitative interviews were held with the parents, peers, and teachers, providing information on precipitating factors and five topics involving 35 cases (17 boys and 18 girls, mean age 17 years). Furthermore, 43 parents and care professionals filled in questionnaires to examine risk and care–related factors. Qualitative and quantitative analyses were performed. Results Although registration problems faced by coroners and resistance to contacting bereaved families by GPs hampered the recruitment, most parents highly appreciated being interviewed. Several adverse childhood experiences played a role at an individual level, such as (cyber) bullying, parental divorce, sexual abuse, as well as complex mental disorders, and previous suicide attempts. Two specific patterns stood out: (1) girls characterized by insecurity and a perfectionist attitude, who developed psychopathology and dropped out of school, and (2) boys with a developmental disorder, such as autism, who were transferred to special needs education and therefore felt rejected. In addition, adolescents with complex problems had difficulty finding appropriate formal care. Regarding potential new trends, contagion effects of social media use in a clinical setting and internet use for searching lethal methods were found. Conclusion This first national PA study showed that, as expected, a variety of mostly complex clusters of problems played a role in youth suicides. An infrastructure is needed to continuously monitor, evaluate, and support families after each youth suicide and thereby improve prevention strategies.