Surveys of parents indicate safety is their top concern about human papillomavirus (HPV) vaccination. A data-mining method not requiring pre-specification of health outcome(s) of interest or post-exposure period(s) of potentially increased risk can check for associations between an exposure and any of thousands of medically attended health outcomes. The method was applied to the 9-valent HPV vaccine (HPV9) to detect potential safety problems. Data on 9-26-year-olds who had received HPV9 vaccine between November 4, 2016 and August 5, 2018, inclusive, were extracted from Marketscan and analyzed for statistically significant clustering of incident diagnoses within the hierarchy of ICD-10-CM coded diagnoses and temporally within the 1 year after vaccination, using the self-controlled tree-temporal scan statistic and TreeScan software. Only 56 days of post-vaccination enrollment was required; subsequent follow-up was censored at disenrollment. Multiple testing was adjusted for. The analysis included 493,089 doses of HPV9. Almost all signals resulted from temporal confounding, not unexpected with a 1-year follow-up period. The only plausible signals were for non-specific adverse events (e.g., injection-site reactions and headache) on Days 1-2 after vaccination, with attributable risks as low as 1 per 100,000 vaccinees. Considering the broad scope of the evaluation and the high statistical power, the findings of no specific serious adverse events should provide reassurance about this vaccine's safety.