A nationwide systematic preparticipation athletic screening was introduced in Italy in 1982. The impact of such a program on prevention of sudden cardiovascular death in the athlete remains to be determined. To analyze trends in incidence rates and cardiovascular causes of sudden death in young competitive athletes in relation to preparticipation screening. A population-based study of trends in sudden cardiovascular death in athletic and nonathletic populations aged 12 to 35 years in the Veneto region of Italy between 1979 and 2004. A parallel study examined trends in cardiovascular causes of disqualification from competitive sports in 42,386 athletes undergoing preparticipation screening at the Center for Sports Medicine in Padua (22,312 in the early screening period [1982-1992] and 20,074 in the late screening period [1993-2004]). Incidence trends of total cardiovascular and cause-specific sudden death in screened athletes and unscreened nonathletes of the same age range over a 26-year period. During the study period, 55 sudden cardiovascular deaths occurred in screened athletes (1.9 deaths/100,000 person-years) and 265 sudden deaths in unscreened nonathletes (0.79 deaths/100,000 person-years). The annual incidence of sudden cardiovascular death in athletes decreased by 89% (from 3.6/100,000 person-years in 1979-1980 to 0.4/100,000 person-years in 2003-2004; P for trend < .001), whereas the incidence of sudden death among the unscreened nonathletic population did not change significantly. The mortality decline started after mandatory screening was implemented and persisted to the late screening period. Compared with the prescreening period (1979-1981), the relative risk of sudden cardiovascular death in athletes was 0.56 in the early screening period (95% CI, 0.29-1.15; P = .04) and 0.21 in the late screening period (95% CI, 0.09-0.48; P = .001). Most of the reduced mortality was due to fewer cases of sudden death from cardiomyopathies (from 1.50/100,000 person-years in the prescreening period to 0.15/100,000 person-years in the late screening period; P for trend = .002). During the study period, 879 athletes (2.0%) were disqualified from competition due to cardiovascular causes at the Center for Sports Medicine: 455 (2.0%) in the early screening period and 424 (2.1%) in the late screening period. The proportion of athletes who were disqualified for cardiomyopathies increased from 20 (4.4%) of 455 in the early screening period to 40 (9.4%) of 424 in the late screening period (P = .005). The incidence of sudden cardiovascular death in young competitive athletes has substantially declined in the Veneto region of Italy since the introduction of a nationwide systematic screening. Mortality reduction was predominantly due to a lower incidence of sudden death from cardiomyopathies that paralleled the increasing identification of athletes with cardiomyopathies at preparticipation screening.