Few studies have explicitly explored the impacts of the extensive adjustment (with a lag period of more than one week) of temperature and humidity on the association between ambient fine particulate matter (PM_2.5) and cardiovascular mortality. In a time stratified case-crossover study, we used a distributed lag nonlinear model to assess the impacts of extensive adjustments of temperature and humidity for longer lag periods (for 7, 14, 21, 28 and 40 days) on effects of PM_2.5 on total cardiovascular mortality and mortality of cerebrovascular and ischemic heart disease and corresponding exposure-response relationships in Beijing, China, between 2008 and 2011. Compared with results only controlled for temperature and humidity for 2 days, the estimated effects of PM_2.5 were smaller and magnitudes of exposure-response curves were decreased when longer lag periods of temperature and relative humidity were included for adjustments, but these changes varied across subpopulation, with marked decreases occurring in males and the elderly who are more susceptible to PM_2.5-related mortalities. Our findings suggest that the adjustment of meteorological factors using lag periods shorter than one week may lead to overestimated effects of PM_2.5. The associations of PM_2.5 with cardiovascular mortality in susceptible populations were more sensitive to further adjustments for temperature and relative humidity.