Background The aim of this study is to determine the rate of persistent negative symptoms according to different criteria during two years of follow-up after first-episode schizophrenia. Methods The study sample consisted of 105 patients with first-episode schizophrenia who completed at least 12months of follow-up period. We used 6 different definitions of persistent negative symptoms (PNS) based on the Scale for the Assessment of Negative Symptoms subscale scores at seven time points throughout the follow-up. In some definitions of PNS, patients with suprathreshold depressive symptoms were excluded. Premorbid adjustment and baseline cognitive performances of the patients were assessed. Results The PNS rates were between 14.2 and 27.9% in the first year and 11.1 and 25.8% in the second year. Seventy-eight percent of the patients who met the strictest PNS criteria during the first 12months met the same criteria also during the second 12-month-period. Those with PNS had earlier onset, lower premorbid functioning, worse executive functioning and attention at baseline, and lower rates of working/studying during the 2-year follow-up. Duration of education and untreated psychosis are the independent variables that contribute to the PNS status at the first year of follow-up in logistic regression analysis. Conclusion Our findings suggest that PNS has specific predictors and effect on the course of illness after first-episode schizophrenia.