Previous research has suggested that professional youth work settings empower socially vulnerable youngsters, strengthening their personal development and social participation. It is expected that youth work can prevent personal and social problems of youngsters, which may have longer term positive social returns. How the underlying methodical way of acting of youth workers contributes to prevention-focused outcomes remains unclear. This article presents a four-wave longitudinal cohort study (16 months) that investigated longitudinal associations between 12 individual methodical principles that youth workers apply in interactions with youngsters and four prevention-focused outcomes: prosocial skills, self-mastery, social network and civic participation. The sample consisted of 1,597 Dutch youngsters with a mean age of 16.5 years (SD = 3.60). Findings: Linear mixed models analysis found that all individual methodical principles were longitudinally associated with one or more outcome. The strongest associations were observed with regard to prosocial skills and civic participation. Depending on the outcome measure, methodical principles seem to be more effective for boys, for youngsters who participate for 3 years or longer in youth work settings and for youngsters between 10 and 19 years old. With regard to the effect of methodical principles on improving self-mastery, 9 of the 12 principles appeared to play no positive role in increasing self-mastery of youngsters. Applications: This study provides youth workers with a better understanding of which methodical principles are positively associated with prevention-focused outcomes as well as reinforcing the evidence-based practice of professional youth work.