PURPOSE: To investigate the effects of clinical, sociodemographic, and occupational factors on time to return to work (RTW) during the 2 years after cancer diagnosis and to analyze whether sex differences exist. PATIENTS AND METHODS: This study was based on a French national cross-sectional survey involving 4,270 cancer survivors. Time to RTW was estimated through the duration of sick leave of 801 cancer survivors younger than 58 years who were employed during the 2-year survey. Multivariate analysis of the RTW after sick leave was performed using a Weibull accelerated failure time model. RESULTS: We found some sex differences in the RTW process. Older men returned to work more slowly than older women (P = .013), whereas married men returned to work much faster than married women (P = .019). Duration dependence was also sex-specific. In men, the time spent on sick leave was independent of the probability of returning to work, whereas in women, this duration dependence was positive (P < .001). For both men and women, clinical factors including chemotherapy, adverse effects, and cancer severity were found to delay RTW (P = .035, P = .001, and P < .001, respectively). Survivors investing most strongly in their personal lives also delayed their RTW (P = .006), as did those with a permanent work contract (P = .042). The factor found to accelerate RTW was a higher educational level (P = .014). CONCLUSION: The RTW process 2 years after cancer diagnosis differed between men and women. A better knowledge of this process should help the national implementation of more cost-effective strategies for managing the RTW of cancer survivors.