Objectives: To investigate causes of death of people with cancer alive five years after diagnosis, and to compare mortality rates for this group with those of the general population. Design, setting, participants: Retrospective cohort study; analysis of South Australian Cancer Registry data for all people diagnosed with cancer during 1990–1999 and alive five years after diagnosis, with follow-up to 31 December 2016. Main outcome measures: All-cause and cancer cause-specific mortality, by cancer diagnosis; standardised mortality ratios (study group v SA general population) by sex, age at diagnosis, follow-up period, and index cancer. Results: Of 32 646 people with cancer alive five years after diagnosis, 30 309 were of European background (93%) and 16 400 were males (50%); the mean age at diagnosis was 60.3 years (SD, 15.7 years). The median follow-up time was 17 years (IQR, 11–21 years); 17 268 deaths were recorded (53% of patients; mean age, 80.6 years; SD, 11.4 years): 7845 attributed to cancer (45% of deaths) and 9423 attributed to non-cancer causes (55%). Ischaemic heart disease was the leading cause of death (2393 deaths), followed by prostate cancer (1424), cerebrovascular disease (1175), and breast cancer (1118). The overall standardised mortality ratio (adjusted for age, sex, and year of diagnosis) was 1.24 (95% CI, 1.22–1.25). The cumulative number of cardiovascular deaths exceeded that of cancer cause-specific deaths from 13 years after cancer diagnosis. Conclusions: Mortality among people with cancer who are alive at least five years after diagnosis was higher than for the general population, particularly cardiovascular disease-related mortality. Survivorship care should include early recognition and management of risk factors for cardiovascular disease.