This study assessed the effectiveness of Individual Placement and Support (IPS), Participatory Workplace Intervention (PWI), and IPS + PWI on work participation and health of people with work disabilities. A randomised controlled 2 × 2 factorial trial with 120 clients and an 18-month follow-up was performed. Differences between IPS and no-IPS and between PWI and no-PWI were assessed using log-rank tests and Cox proportional hazards models. In the IPS group, restricted mean survival time (RMST) for sustainable paid employment was 352days, compared to 394 in the no-IPS group (HR = 1.47, 95% CI = 0.81-2.63). In the PWI group the RMST was 378days, compared to 367 in the no-PWI group (HR = 0.89, 95% CI = 0.48-1.64). For the secondary outcome 'starting any paid employment, a trial placement, or education' RMST was significantly lower for the IPS group (222days) than for the no-IPS group (335days; HR = 1.85, 95% CI = 1.01-3.42). Mental health was significantly lower (worse) in the PWI group (difference -4.07, 95% CI = -7.93 to -0.22) than in the no-PWI group. For all other secondary outcomes, no statistically significant differences were found. No statistically significant differences were observed in the duration until starting sustainable employment between IPS and no-IPS, and between PWI and no-PWI. The duration until starting any paid employment, a trial placement, or education was shorter in the IPS group than in the no-IPS group, but further research should explore whether this also increases sustainable employment in the longer term.