Purpose: To compare the outcome of patients with Stage II seminoma treated with prophylactic mediastinal irradiation, without any supradiaphragmatic irradiation, and with prophylactic left supraclavicular irradiation (PLSCI).Methods and Materials: Between 1960 and 1999, 73 men with Stage II seminoma received postorchiectomy radiotherapy. Before 1984, 36 received prophylactic mediastinal irradiation (Series I); between 1984 and 1992, 17 received no supradiaphragmatic irradiation (Series II); and after 1992, 20 received PLSCI (Series III). The outcomes in these series were compared.Results: The abdominal tumor sizes were as follows: Series I, ≤2 cm, n = 4; >2 and ≤5 cm, n = 12; >5 and ≤10 cm, n = 16; Series II, ≤2 cm, n = 1; >2 and ≤5 cm, n = 12; >5 and ≤10 cm, n = 4; and Series III, ≤2 cm, n = 1; >2 and ≤5 cm, n = 14; >5 and ≤10 cm, n = 5 (p = 0.75). The median duration of follow-up was 14.4, 9.3, and 4.5 years for Series I, II, and III, respectively. The 6-year freedom from relapse was 94%, 71%, and 95% for Series I, II, and III, respectively. The differences between Series I and II (p = 0.014) and between II and III (p = 0.042) were significant. Three patients in Series II had a relapse in their left supraclavicular fossa—a failure pattern abrogated by PLSCI.Conclusions: PLSCI significantly diminishes the likelihood of relapse for Stage IIA, IIB, and IIC seminoma (mass ≤10 cm).