Objective: To describe trends in incidence of high-grade vaginal intraepithelial neoplasia (VaIN) and vaginal squamous cell carcinoma (SCC) in Denmark. For vaginal SCC, we also examine 5-year relative survival and mortality. Methods: All high-grade VaIN cases diagnosed 1997–2017 and vaginal SCCs during 1978–2017 were identified in two high-quality nationwide registers. Age-standardized incidence rates and average annual percentage change (AAPC) were assessed. For vaginal SCC, 5-year relative survival was calculated, and Cox regression was applied to study the effect of selected characteristics on mortality. Results: Altogether, 831 cases of high-grade VaIN and 721 vaginal SCCs were identified. The age-standardized incidence rate of high-grade VaIN showed no clear trend over time. However, when we stratified by age and divided the study period according to HPV vaccine licensure in Denmark (2006), the incidence of high-grade VaIN decreased significantly by 15.6% per year (95% CI: −23.2, −7.3%) after 2007 onwards among the youngest women (<30 years). For vaginal SCC, the incidence decreased from 0.5 (1978–1982) to 0.3 (2013–2017) per 100,000 woman-years. The 5-year relative survival improved over time and was 67.9% (95% CI: 54.9, 84.1%) in the most recent time period. Mortality was significantly associated with calendar year, age, and stage at diagnosis. Conclusions: The overall incidence of high-grade VaIN showed no clear trend over time, but a significant decline was observed in women younger than 30 years after HPV vaccine licensure. The incidence of vaginal SCC was reduced by approximately 50% and survival after vaginal SCC improved over time.