Aim: Many individuals with schizophrenia discontinue initially prescribed antipsychotics. Knowledge on reasons for discontinuation among individuals with first-episode schizophrenia is sparse. We aimed to describe reasons for discontinuation and continuation, differences between individuals discontinuing and continuing, and factors predicting reasons for discontinuation or continuation. Methods: This was a prospective cohort study with a post hoc design. Individuals with first-episode schizophrenia were included from early intervention teams in Denmark from 2009–2012. Sociodemographic and clinical variables were collected at baseline and reasons for discontinuation and continuation of antipsychotics were assessed at 3.5-year follow-up. Results: Among 215 patients, 76 reported reasons for discontinuation and 139 for continuation. The most frequent reasons for discontinuation were “side effects” and “patient believed he/she no longer needed the medication because he/she was now better”. The most frequent reasons for continuation were “benefits for positive symptoms” and “another person told them to”. Individuals who discontinued antipsychotics were at baseline younger, had longer DUP, less negative symptoms, better social function, lower compliance, higher self-belief of coping, and fewer used antipsychotics compared to those continuing antipsychotics. Conclusions: The effect of antipsychotics is the main reason to continue, whereas side effects were the main reason to discontinue. Knowledge of reasons to discontinue or continue is helpful in shared decision-making, identifying individuals with high odds of discontinuation, improving adherence, and helping with safe discontinuation.