Background: When handling patients, nursing assistant (NA) students and nurse students are frequently exposed to risk factors for low back pain (LBP) including sudden loads and twisting and bending of the spine. Furthermore, LBP is a major cause of sickness absence. Aims: To ascertain if a multidimensional prevention programme combining physical training, patient transfer technique and stress management prevents sickness absence and LBP in NA students. Methods: The study was a 14-month cluster randomized controlled study. The participants were NA students from 37 randomly selected classes located at two schools of health and social care in Copenhagen, Denmark. The participants completed a comprehensive questionnaire regarding sickness absence, LBP and psychosocial factors on commencement and after completion of the study. Results: Of 766 female NA students, 668 (87%) completed the baseline questionnaire. Sickness absence during the study period increased in both groups but the increase was significantly lower in the intervention group than the control group, mean (standard deviation) number of days 12 (20) versus 18 (34), P < 0.05. The intervention group reported no change in the mean level of general health perception, energy/fatigue or psychological well-being at follow-up, while the control group reported a decline on those scales. There were no significant differences in the prevalence of LBP at follow-up between the intervention and control group. Conclusions: Compared to the control group, the intervention group had significantly less sickness absence. The intervention had no preventive effect on LBP prevalence.