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Purpose The aims of this study are to investigate the course of work functioning, health status, and work-related factors among cancer patients during 18 months after return to work (RTW) and to examine the associations between these variables and work functioning over time. Methods Data were used from the 18-month longitudinal “Work Life after Cancer” (WOLICA) cohort, among 384 cancer patients who resumed work. Linear mixed models were performed to examine the different courses during 18-month follow-up. Linear regression analyses with generalized estimating equations (GEE) were used to examine the associations and interactions. Results Cancer patients reported an increase of work functioning and a decrease of fatigue and depressive symptoms in the first 12 months, followed by a stable course between 12 and 18 months. Cognitive symptoms were stable during the first 18 months. Working hours increased and social support decreased during the first 6 months; both remained stable between 6 and 18 months. Fatigue, depressive, and cognitive symptoms were negatively associated with work functioning over time; working hours and supervisor social support were positively associated. Conclusions Interventions to improve cancer patients’ work functioning over time might be promising if they are aimed at reducing fatigue, depressive symptoms, cognitive symptoms, and encouraging supervisor social support. Implications for Cancer Survivors It is important to monitor cancer patients not only in the period directly after RTW but up to 18 months after RTW, allowing for timely interventions when needed.