Health-related quality of life (HRQOL) is an increasingly important patient-reported outcome in kidney transplant recipients (KTRs). This study explored relationships between symptom prevalence and burden with HRQOL, and age and gender differences in symptom experience. Eligible Dutch KTRs transplanted in Leiden University Medical Center were invited for this cross-sectional study. HRQOL, and occurrence and burden of 62 symptoms were measured using validated questionnaires. Univariate and multivariate regression analysis were used for investigating the associations of symptom experience with mental and physical HRQOL, and differences in symptom experience between genders and KTRs of diverse age groups. A total of 631 KTRs were analyzed; the mean (standard deviation) age was 61.3 (11.3) years, and 62% were male. The median (interquartile range) number of symptoms was 14 (7-22), with a burden of 20 (8-37; range 0-244). Per extra symptom, physical and mental HRQOL decreased [-0.41 (-0.50; -0.31) and -0.51 (-0.59; -0.42), respectively, P<.001]. Most occurring symptoms were bruises, tiredness, lack of energy, urge to urinate at night and dry skin. Sexual problems were considered most burdensome. Female KTRs reported more symptoms than men. Amongst others, younger KTRs experienced more (18-50>50-65≥65 years) feelings of depression and both female and younger KTRs reported higher symptom prevalence concerning changes in physical appearance. KRTs' symptom experience differed depending on gender and age, highlighting the need to develop tailored treatment strategies to reduce symptom experience and subsequently improve HRQOL.