Background We examined: (i) the usefulness of the International Fitness Scale (IFIS) to correctly rank adolescents into physical fitness levels; (ii) the capacity of the IFIS for predicting cardiovascular disease (CVD) risk; and (iii) the reliability of the IFIS in adolescents. Methods The study comprised 3059 adolescents (aged 12.5-17.5 years) from nine European countries (HELENA study). Blood samples were collected in one-third of the participants (randomly selected, n = 981). Test-retest reliability of the IFIS was studied in a separate sample of 277 adolescents. Physical fitness-cardiorespiratory fitness (CRF), muscular fitness (MF), speed-agility (SP-AG), flexibility and overall fitness-was self-reported using 5-point Likert-scale questions (1 = very poor, 5 = very good) and measured using standard field-based tests. The CVD risk factors measured included total/central adiposity indices and mean arterial pressure, total and high density lipoprotein cholesterol, triglycerides, insulin resistance (HOMA) and C-reactive protein. Results Analysis of covariance showed that adolescents reporting better fitness had higher measured fitness levels for all the variables studied (all P < 0.001), regardless of gender, age and weight status. Adolescents reporting very good overall fitness, CRF and SP-AG had a healthier cardiovascular profile in eight out of nine CVD risk factors studied. Perfect agreement (same test-retest answer) was observed in 65% of the adolescents and perfect-acceptable agreement (same answer or ±1) in 97% of the adolescents. Conclusions (i) The IFIS is able to correctly rank adolescents according to their measured physical fitness levels; (ii) adolescents reporting a good/very good overall fitness, CRF or SP-AG have a more favorable cardiovascular profile; and (iii) The IFIS is reliable in adolescents.