The "Spanish Ketogenic Mediterranean Diet" (SKMD) has been shown to promote potential therapeutic properties for the metabolic syndrome. The purpose of this study was to evaluate the potential therapeutic properties under free-living conditions of the SKMD in patients with metabolic syndrome (following the International Diabetes Federation consensus guidelines) over a 12-week period. A prospective study was carried out in 22 obese subjects with metabolic syndrome (12 men and 10 women) with the inclusion criteria whose body mass index of 36.58 ± 0.54 kg/m² and age was 41.18 ± 2.28 years. Statistical differences between the parameters studied before and after the administration of the SKMD (week 0 and 12, respectively) were analyzed by paired Student's t test. There was an extremely significant (P < .001) improvement in low-density lipoprotein cholesterol (from 126.25 mg/dL to 103.87 mg/dL) and all the parameters studied associated with metabolic syndrome: body weight (from 106.41 kg to 91.95 kg), body mass index (from 36.58 kg/m² to 31.69 kg/m²), waist circumference (from 111.97 cm to 94.70 cm), fasting plasma glucose (from 118.81 mg/dL to 91.86 mg/dL), triacylglycerols (from 224.86 mg/dL to 109.59 mg/dL), high-density lipoprotein cholesterol (from 44.44 to 57.95 mg/dL), systolic blood pressure (from 141.59 mm Hg to 123.64 mm Hg), and diastolic blood pressure (from 89.09 mm Hg to 76.36 mm Hg). The most affected parameter was the triacylglycerols (51.26% reduction). After the diet all the subjects were free of metabolic syndrome according to the International Diabetes Federation definition, and 100% of them had normal triacylglycerols and high-density lipoprotein cholesterol levels, in spite of the fact that 77.27% of them still had a body mass index of > 30 kg/m². We conclude that the SKMD could be an effective and safe way to cure patients suffering from metabolic syndrome. Future research should include a larger sample size, a longer-term use, and a comparison with other ketogenic diets.