<$O_ST_ABS>Background.<$C_ST_ABS>Little is known about pediatric Clostridium difficile infection (CDI) epidemiology. We describe the clinical and microbiological characteristics of CDI among hospitalized children in the Netherlands. <$O_ST_ABS>Methods.<$C_ST_ABS>Between May 2009 and May 2015, 26 hospitals registered characteristics of pediatric (aged 2–18 years) and adult (aged 18 years) CDI in a national sentinel surveillance study. Routine polymerase chain reaction (PCR) ribotyping and multiple-locus variable-number tandem-repeat analysis (MLVA) of selected strains was performed. Pediatric and adult results were compared using proportion and 95% confidence interval (CI). Time trend of pediatric CDI was evaluated using a mixed-effect Poisson model. <$O_ST_ABS>Results.<$C_ST_ABS>Pediatric CDIs were reported in 17 of the 26 participating hospitals (n = 135; 3% of all CDIs); the monthly number was constant over time. The median age of pediatric cases was 10 years (interquartile range, 4.7–14.5 years). Fifty-five percent of the children had community onset and 31% had severe CDI. Compared with adults (n = 4,556), complication and mortality rates were lower. Clostridium difficile PCR ribotype 265 (toxin A negative, B positive) was most prevalent in children (15%; 95% CI, 8.8%–24.0%) but rarely found in adults (1%; 95% CI, 0.9%–1.6%). This strain was rarely found in other countries, except for Belgium. MLVA showed genetic relatedness between three-fourths of pediatric and adult ribotype 265 strains, without a clear epidemiological link. <$O_ST_ABS>Conclusions.<$C_ST_ABS>Pediatric CDI in hospitals has remained stable over the last 6 years and resulted in fewer complications than for adult CDI. Further studies are needed to elucidate the source and epidemiology of PCR ribotype 265, primarily found in children.