This study examined symptom change trajectories during inpatient psychotherapy and the association of these changes with long-term outcomes. In an observational multicenter study, weekly measurements of symptom severity were performed during inpatient treatment and 6 months after discharge. The symptom severity was measured using the 18-item scale of the Hamburg Modules for the Assessment of Psychosocial Health. The sample included 576 inpatients (mean age: 43.9 years; 77.6% female; main diagnoses: depressive (57.2%), adjustment (15.8%), anxiety (7.4%), and eating disorders (7.2%); mean treatment duration: 42.0 days). With empirically and clinically informed growth mixture models four subgroups of symptom change were revealed: gradual response (71%), early response (9%), delayed response (5%), and nonresponse (11%). Particularly low educational level, non-employment and chronic disorders were associated with unfavorable symptom courses (non- and delayed response). Long-term outcomes differed systematically across subgroups (p<0.001; η(2)=0.165). The patients who responded early presented the highest rates of clinically significant improvement (43.9%) from admission to follow-up. Nearly all of these patients (92.7%) showed reliable improvement. Due to the high association of symptom change trajectories with long-term outcomes, results may contribute to interventions that are tailored to the needs of patients and may foster longer lasting therapeutic effectiveness.