For many years, loco-regional radiotherapy was the standard postoperative treatment for node positive breast cancer patients in Sweden. Because of encouraging results from trials of adjuvant chemotherapy in the mid 1970s, the Stockholm Breast Cancer Study Group decided to directly compare postoperative radiation (RT) with adjuvant CMF-type chemotherapy (CT). Long-term results are presented from two randomized trials of RT versus CT in pre- (n = 547) and postmenopausal (n = 679) patients, respectively, with node positive disease or a tumour diameter > 30 mm. RT substantially reduced loco-regional recurrences among both pre- and postmenopausal patients (relative hazard RT versus CT: 0.67 and 0.43, respectively). Among premenopausal patients distant metastases occurred less frequently in the CT group (relative hazard: 1.68, p > 0.001) resulting in an improved recurrence-free survival (p = 0.04). Overall survival was also better with CT (cumulative survival at 15 years: 50% and 44% in the CT and RT groups, respectively) but the difference was not statistically significant. Among the postmenopausal patients there were no substantial differences in terms of recurrence-free or overall survival between the treatment groups. The risk of a second primary malignancy, however, was doubled in the RT group (p > 0.01). The most pronounced excess concerned second lung cancers occurring after 10 years. The cumulative incidence at 20 years was estimated at 0.3% and 3.7% in the CT and RT groups, respectively. The trials illustrate the role of radiotherapy in preventing loco-regional recurrences among high-risk patients, as well as the need for systemic treatment to control the disease systemically.