BACKGROUND: The COVID-19 pandemic has affected people's engagement in health behaviors, especially those that protect individuals from SARS-CoV-2 transmission, such as handwashing/sanitizing. This study investigated whether adherence to the World Health Organization's (WHO) handwashing guidelines (the outcome variable) was associated with the trajectory of the COVID-19 pandemic, as measured by the following 6 indicators: (i) the number of new cases of COVID-19 morbidity/mortality (a country-level mean calculated for the 14 days prior to data collection), (ii) total cases of COVID-19 morbidity/mortality accumulated since the onset of the pandemic, and (iii) changes in recent cases of COVID-19 morbidity/mortality (a difference between country-level COVID-19 morbidity/mortality in the previous 14 days compared to cases recorded 14-28 days earlier). METHODS: The observational study (#NCT04367337) enrolled 6064 adults residing in Australia, Canada, China, France, Gambia, Germany, Israel, Italy, Malaysia, Poland, Portugal, Romania, Singapore, and Switzerland. Data on handwashing adherence across 8 situations (indicated in the WHO guidelines) were collected via an online survey (March-July 2020). Individual-level handwashing data were matched with the date- and country-specific values of the 6 indices of the trajectory of COVID-19 pandemic, obtained from the WHO daily reports. RESULTS: Multilevel regression models indicated a negative association between both accumulation of the total cases of COVID-19 morbidity (B = -.041, SE = .013, p = .013) and mortality (B = -.036, SE = .014 p = .002) and handwashing. Higher levels of total COVID-related morbidity and mortality were related to lower handwashing adherence. However, increases in recent cases of COVID-19 morbidity (B = .014, SE = .007, p = .035) and mortality (B = .022, SE = .009, p = .015) were associated with higher levels of handwashing adherence. Analyses controlled for participants' COVID-19-related situation (their exposure to information about handwashing, being a healthcare professional), sociodemographic characteristics (gender, age, marital status), and country-level variables (strictness of containment and health policies, human development index). The models explained 14-20% of the variance in handwashing adherence. CONCLUSIONS: To better explain levels of protective behaviors such as handwashing, future research should account for indicators of the trajectory of the COVID-19 pandemic. TRIAL REGISTRATION: Clinical Trials.Gov, # NCT04367337.