Background Little is known about the associations of different depths of individualization of the exercise intervention on cardiorespiratory fitness (CRF), metabolic outcomes and cardiac autonomic regulation in at-risk subjects. This randomized trial compared the effect of general physical activity (PA) guideline -targeted and highly individualized exercise intervention on maximal oxygen uptake, heart rate variability, body composition, and glucose and lipid profiles in fertile-aged women with increased risk for gestational diabetes. Methods Forty-five women with previous gestational diabetes or BMI>30kg/m 2 were randomized into general advice without intervention (Group 1), individualized intervention planned according to PA questionnaires and general guidelines for exercise training (Group 2) and highly individualized intervention based on results from the pre-intervention cardiopulmonary exercise test (CPET) groups (Group 3). All subjects performed pre-intervention CPET on a cycle ergometer with step incremental protocol until volitional fatigue, followed by a 3-month intervention period and post-intervention CPET. Examinations included HRV assessment during CPET and body composition (bioimpedance), blood glucose and lipid profiles. Results Total dropout was 53.8% at various points of the study leaving 8 subjects in Group 1, 12 subjects in Group 2 and 10 subjects in Group 3. CRF improved only in Group 3 (+1.9 ml/kg/min, 95% CI 0.3 to 3.5). This was associated with an increase in high-density lipoprotein (0.18 mmol/L, 95% CI 0.04 to 0.32) and increased HRV. In Group 2, we found a decrease in body mass index (-0.7 kg/m 2, 95% CI -1.3 to -0.1), fasting insulin (-4.14 mU/L, 95% CI -6.58 to -1.70), insulin resistance (-1.21, 95% CI -1.88 to -0.54), and low-density lipoprotein (-0.44 mmol/L, 95% CI -0.79 to -0.09). The dropouts in Group 1 had significantly less weight, smaller waist circumference, less visceral fat, and higher maximal oxygen uptake compared to the continuers in Group 1. Conclusions To improve CRF and cardiac autonomic function the exercise intervention should be highly individualized. PA intervention focused to achieve general exercise guidelines is not enough to improve CRF over 3-month period but combined with weight loss has beneficial effects on the metabolic profile. In randomized controlled trials, dropout may be biased. Trial Registration clinicaltrials.gov (NCT01675271)