Background <p>Practice assignments (i.e., homework) are a key component of evidence-based treatment for posttraumatic stress disorder (PTSD), including cognitive processing therapy (CPT). Practice assignments putatively promote symptom change, but symptom improvement may also promote engagement with assignments (i.e., adherence) and positive attributions (i.e., perceived helpfulness).</p> Method <p>This study used cross-lagged multilevel models and disaggregated between- and within-person effects to examine the temporal relationships between practice assignments (adherence; helpfulness) and symptom changes (PTSD; depression) during treatment. Participants were 77 service members with comorbid PTSD and major depressive disorder who received CPT or behavioral activation-enhanced CPT in a randomized clinical trial.</p> Results <p>Disaggregated models revealed reciprocal relationships between PTSD and depression symptoms and practice assignment helpfulness, with lagged effects in both directions primarily explained by between-person, rather than within-person, variability (<i>d</i>s =  − 0.41 to − 0.62). A single, unexpected within-person lagged effect was observed, where increases in depression symptoms were associated with subsequent increases in helpfulness ratings (<i>d</i> = 0.44). In all models, treatment condition did not moderate relationships.</p> Conclusions <p>Findings reinforce the utility of assessing patients’ perceived helpfulness of practice assignments during treatment. However, helpfulness may be related to other processes associated with symptom reduction rather than a salient change mechanism itself.</p>