Objective: The aim of the study was to explore the extent to which initial severity of positive or negative symptoms in patients with recent-onset schizophrenia is related to medication nonadherence during the first outpatient year. Methods: The study involved 64 first-episode schizophrenia patients treated with the second-generation oral antipsychotic medication, risperidone, for 12. months. Symptoms were evaluated using the SANS and SAPS completed every 3. months. Pearson correlations between medication adherence and symptoms were examined over each 3-month interval during 12. months of follow-through treatment. Possible causality was inferred from cross-lagged panel analyses. Results: As expected, higher levels of adherence with antipsychotic medication were generally associated with lower levels of concurrent reality distortion (mean of SAPS delusions and hallucinations). Greater adherence during the 3-month baseline interval was generally associated with lower levels of avolition-apathy as well as alogia throughout the first outpatient year. However, medication adherence was not significantly associated with decreases in avolition-apathy or alogia over time. Cross-lagged panel analyses based on correlation coefficients are consistent with a causal relationship between initial medication adherence and lower levels of alogia. A test of mediation confirmed that an indirect path through reality distortion mediated the relationship between medication nonadherence and alogia. Conclusions: The associations between greater medication adherence and lower levels of negative symptoms appeared to be accounted for by the relationship of both variables to positive psychotic symptoms. The findings suggest that the impact of second-generation antipsychotic medication on suppression of negative symptoms might be mediated via a reduction in positive symptoms.