Musculoskeletal injuries among health care workers are very high, particularly so in nurses involved in patient handling. Efforts to reduce injuries have shown mixed results, and strong evidence for intervention effectiveness is lacking.The purpose of our study was to evaluate the effectiveness ofa Transfer, Lifting and Repositioning (TLR) program to re- duce musculoskeletal injuries (MSI) among direct health care workers. This study was a pre- and post-intervention design, utilizing a nonrandomized control group. Data were collected from the intervention group (3 hospitals; 411 injury cases) and the control group (3 hospitals; 355 injury cases) for periods1 year pre- and post-intervention. Poisson regression analyseswere performed. Of a total 766 TLR injury cases, the majority of injured workers were nurses, mainly with back, neck, and shoulder body parts injured. Analysis of all injuries andtime-loss rates (number of injuries/100 full-time employees),rate ratios, and rate differences showed significant differences between the intervention and control groups. All-injuries rates for the intervention group dropped from 14.7 pre-intervention to 8.1 post-intervention. The control group dropped from 9.3to 8.4. Time-loss injury rates decreased from 5.3 to 2.5 in theintervention group and increased in the control group (5.9 to 6.5). Controlling for group and hospital size, the relative rate of allinjuries and time-loss injuries for the pre- to post-period decreased by 30% (RR = 0.693; 95% CI = 0.60–0.80) and 18.6% (RR = 0.814; 95% CI = 0.677–0.955), respectively. The study provides evidence for the effectiveness of a multifactorTLR program for direct care health workers, especially in smallhospitals