Interactions between phospholipid vesicles and poly(acrylic acid) (PAA) are of fundamental importance for pH-sensitive delivery systems in pharmaceutical applications. In this study, we investigated the behavior of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) at varied concentrations of PAA with low and high molecular weights. Differential scanning calorimetry and fluorescence microscopy experiments suggested that hydrogen bonding between the carboxyl group of PAA and the phosphodiester group of the lipid is the main driving force for association under acidic conditions. Complexation between DPPC and PAA depends on the PAA molecular weight and concentration. At high enough concentrations of the large molecular weight PAA, the polymer can completely disrupt the bilayers of DPPC. For the small molecular weight PAA, in contrast, the complexation leads to vesicle aggregation without destroying the bilayers. The difference in complex structure was detected by SEM and a UV-visible spectrophotometer. At alkaline pH, complexation did not occur because of strong dissociation of PAA.