Pulpectomy may be indicated in restorable primary teeth exhibiting irreversible pulpitis or pulpal necrosis. The purpose of this study was to compare the cleaning and shaping efficacy of NiTi systems (Reciproc® Blue and MTwo®) with manual stainless-steel instrumentation in primary molars using micro-CT analysis. Fifty-seven maxillary second primary molars were scanned using micro-CT. Teeth with three divergent roots were divided randomly (n = 15) according to instrument type (K file, MTwo®, and Reciproc® Blue). Teeth with root fusion were instrumented manually as a separate group (n = 12). Pre- and post-instrumentation micro-CT images were superimposed, and the instrumentation area (IA) and procedural complications were recorded. No statistically significant differences in IA between file systems was observed in the non-fused teeth. The mean IA of fused roots was significantly lower than in the non-fused distobuccal (p = 0.003) and palatal (p < 0.001) roots. The root segment had a significant effect on IA (p < 0.001) and the highest mean IA was observed in the apical third. Manual instrumentation had fewer procedural complications compared with rotary systems. No differences were determined in the cleaning and shaping effectiveness of all systems in non-fused teeth. Uninstrumented areas (> 60%) occurred in both non-fused and fused primary teeth with fewer procedural complications observed after manual instrumentation.