Management of the open abdomen is a considerable burden for patients and healthcare professionals. Various temporary abdominal closure techniques have been suggested for managing the open abdomen. In recent years, negative pressure wound therapy (NPWT) has been used in some centres for the treatment of non-trauma patients with an open abdomen; however, its effectiveness is uncertain. To assess the effects of negative pressure wound therapy (NPWT) on primary fascial closure for managing the open abdomen in non-trauma patients in any care setting. In October 2021 we searched the Cochrane Wounds Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL EBSCO Plus. To identify additional studies, we also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses, and health technology reports. There were no restrictions with respect to language, date of publication, or study setting. We included all randomised controlled trials (RCTs) that compared NPWT with any other type of temporary abdominal closure (e.g. Bogota bag, Wittmann patch) in non-trauma patients with open abdomen in any care setting. We also included RCTs that compared different types of NPWT systems for managing the open abdomen in non-trauma patients. Two review authors independently performed the study selection process, risk of bias assessment, data extraction, and GRADE assessment of the certainty of evidence. We included two studies, involving 74 adults with open abdomen associated with various conditions, predominantly severe peritonitis (N = 55). The mean age of the participants was 52.8 years; the mean proportion of women was 39.2%. Both RCTs were carried out in single centres and were at high risk of bias. Negative pressure wound therapy versus Bogota bag We included one study (40 participants) comparing NPWT with Bogota bag. We are uncertain whether NPWT reduces time to primary fascial closure of the abdomen (NPWT: 16.9 days versus Bogota bag: 20.5 days (mean difference (MD) -3.60 days, 95% confidence interval (CI) -8.16 to 0.96); very low-certainty evidence) or adverse events (fistulae formation, NPWT: 10% versus Bogota: 5% (risk ratio (RR) 2.00, 95% CI 0.20 to 20.33); very low-certainty evidence) compared with the Bogota bag. We are also uncertain whether NPWT reduces all-cause mortality (NPWT: 25% versus Bogota bag: 35% (RR 0.71, 95% CI 0.27 to 1.88); very low-certainty evidence) or length of hospital stay compared with the Bogota bag (NPWT mean: 28.5 days versus Bogota bag mean: 27.4 days (MD 1.10 days, 95% CI -13.39 to 15.59); very low-certainty evidence). The study did not report the proportion of participants with successful primary fascial closure of the abdomen, participant health-related quality of life, reoperation rate, wound infection, or pain. Negative pressure wound therapy versus any other type of temporary abdominal closure There were no randomised controlled trials comparing NPWT with any other type of temporary abdominal closure. Comparison of different negative pressure wound therapy devices We included one study (34 participants) comparing different types of NPWT systems (Suprasorb CNP system versus ABThera system). We are uncertain whether the Suprasorb CNP system increases the proportion of participants with successful primary fascial closure of the abdomen compared with the ABThera system (Suprasorb CNP system: 88.2% versus ABThera system: 70.6% (RR 0.80, 95% CI 0.56 to 1.14); very low-certainty evidence). We are also uncertain whether the Suprasorb CNP system reduces adverse events (fistulae formation, Suprasorb CNP system: 0% versus ABThera system: 23.5% (RR 0.11, 95% CI 0.01 to 1.92); very low-certainty evidence), all-cause mortality (Suprasorb CNP system: 5.9% versus ABThera system: 17.6% (RR 0.33, 95% CI 0.04 to 2.89); very low-certainty evidence), or reoperation rate compared with the ABThera system (Suprasorb CNP system: 100% versus ABThera system: 100% (RR 1.00, 95% CI 0.90 to 1.12); very low-certainty evidence). The study did not report the time to primary fascial closure of the abdomen, participant health-related quality of life, length of hospital stay, wound infection, or pain. Based on the available trial data, we are uncertain whether NPWT has any benefit in primary fascial closure of the abdomen, adverse events (fistulae formation), all-cause mortality, or length of hospital stay compared with the Bogota bag. We are also uncertain whether the Suprasorb CNP system has any benefit in primary fascial closure of the abdomen, adverse events, all-cause mortality, or reoperation rate compared with the ABThera system. Further research evaluating these outcomes as well as participant health-related quality of life, wound infection, and pain outcomes is required. We will update this review when data from the large studies that are currently ongoing are available.