Purpose Studies have demonstrated improvements in hand hygiene (HH) compliance through interventions, noting the negative association of HH and healthcare associated infections (HAIs), but how to sustain long-term improvement is still unknown in the Chinese population. This study sought to determine the extent of change in HH compliance after multimodal HH interventions, and to evaluate the relationship between that change and HAI incidence. Methods We conducted a longitudinal study in a general teaching hospital in China from 2017 to 2020. Trained investigators observed HH practices based on the World Health Organization's 5 moments for HH. We identified the incidence of HAIs using semi-automated constant surveillance software. We used the Cochran-Mantel-Haenszel test to assess the secular trend of HH compliance and HAIs. The Spearman correlation coefficient (r s ) was used to evaluate the relationship between the incidence of HAIs and compliance with HH. Results The study made 480,943 observations, where HH was occurring between 2017 and 2020. HH compliance increased from 68.90 to 91.76% during that period (P trend < 0.01), while the incidence of HAIs decreased from 1.10 to 0.91%. Compliance also increased for each moment type and for each healthcare worker (P trend < 0.01). Lower HH compliance was observed in before-patient contact and after contact with patient surroundings, and among interns and cleaners. We also observed a weak but statistically significant negative correlation between the monthly HH compliance and incidence of HAIs (r s = − 0.27; P = 0.037). Conclusions The multimodal HH implementation delivered sustained improvement in HH compliance, and this change was associated with a decline in the incidence of HAIs.