Many treatments for pressure ulcers are promoted, but their relative efficacy is unclear. To systematically review published randomized controlled trials (RCTs) evaluating therapies for pressure ulcers. The databases of MEDLINE, EMBASE, and CINAHL were searched (from inception through August 23, 2008) to identify relevant RCTs published in the English language. Methodological characteristics and outcomes were extracted by 3 investigators. A total of 103 RCTs met inclusion criteria. Of these, 83 did not provide sufficient information about authors' potential financial conflicts of interest. Methodological quality was variable. Most trials were conducted in acute care (38 [37%]), mixed care (25 [24%]), or long-term care (22 [21%]) settings. Among 12 RCTs evaluating support surfaces, no clear evidence favored one support surface over another. No trials compared a specialized support surface with a standard mattress and repositioning. Among 7 RCTs evaluating nutritional supplements, 1 higher-quality trial found that protein supplementation of long-term care residents improved wound healing compared with placebo (improvement in Pressure Ulcer Scale for Healing mean [SD] score of 3.55 [4.66] vs 3.22 [4.11], respectively; P < .05). Other nutritional supplement RCTs showed mixed results. Among 54 RCTs evaluating absorbent wound dressings, 1 found calcium alginate dressings improved healing compared with dextranomer paste (mean wound surface area reduction per week, 2.39 cm(2) vs 0.27 cm(2), respectively; P<.001). No other dressing was superior to alternatives. Among 9 RCTs evaluating biological agents, several trials reported benefits with different topical growth factors. However, the incremental benefit of these biological agents over less expensive standard wound care remains uncertain. No clear benefit was identified in 21 RCTs evaluating adjunctive therapies including electric current, ultrasound, light therapy, and vacuum therapy. Little evidence supports the use of a specific support surface or dressing over other alternatives. Similarly, there is little evidence to support routine nutritional supplementation or adjunctive therapies compared with standard care.