The objective of the study was to gain insight into the effectiveness of vacuum-assisted closure (VAC) therapy or, more particularly, topical negative pressure (TNP) in the treatment of pressure ulcers. We carried out a systematic search in Medline, Embase and Cinahl for Randomized Clinical Trials (RCTs) involving topical negative pressure in pressure ulcers over the period 1992–2007. Five RCTs were included. Two studies dealt exclusively with pressure ulcers. No significant differences in wound healing were found in these studies. Three other studies (mixed etiology of wounds) did show significant differences in wound healing, in the decrease of wound treatment time, and in the decrease in number of bacteria. The quality of these studies, both in terms of methodology and otherwise, did not always match with the scientific standard. Moreover, these studies lacked subgroup analyses. The analyzed studies described positive effects of TNP, although both the control treatment and the end points varied in these studies. On the basis of the systematic assessment of these five RCTs, the conclusion is that TNP has not proven to be more effective than various control interventions. The differences between and within the studies in terms of control interventions, the differences in randomization and a number of weaknesses in the analyses do not allow a good comparison. The main recommendations for follow-up studies include: randomization of patients rather than of wounds, a homogeneous patient population, the use of a single well-defined and procedurally documented control intervention, and prior calculation of the random sample size.