Objective: This study examined the effect of medication nonadherence on the return of positive symptoms among recent-onset schizophrenia patients. Method: Three sets of operational criteria for medication nonadherence with differing levels of severity were compared for their ability to predict relapse. Explicit operational criteria are provided with the hope that they will be adopted by others. Psychotic symptoms were prospectively rated on a frequent basis, and systematic criteria were applied using a computer scoring program to identify periods of psychotic symptom return. In addition, a specialized statistical survival analysis method, optimal for examining risk periods and outcomes that can recur during the follow-up assessment, was used. Results: As hypothesized, medication nonadherence robustly predicted a return of psychotic symptoms during the early phase of schizophrenia (hazard ratios=3.7-28.5, depending on the severity of nonadherence). Conclusions: Even brief periods of partial nonadherence lead to greater risk of relapse than what is commonly assumed. Patients in the early phase of schizophrenia should be cautioned about the possible consequences of partial or relatively brief periods of antipsychotic medication nonadherence.