This prospective study aimed to evaluate the success rate of partial pulpotomy using mineral trioxide aggregate (MTA), in permanent molars with symptomatic irreversible pulpitis. Moreover, this study aimed to investigate the effect of carious lesion depth and activity and bleeding time on the outcome of partial pulpotomy. Forty permanent molars with deep and extremely deep carious lesions clinically diagnosed with symptomatic irreversible pulpitis were included. The status of the carious lesion was evaluated clinically and radiographically to determine its activity (rapidly or slowly progressing) and depth (deep or extremely deep). A partial pulpotomy was performed and MTA was used. Clinical and radiographic analysis were performed at 3, 6 and 12 months. Chi-square analysis and Fisher’s exact test were used. Scanning electron microscope and energy dispersive X-rays were used to investigate the crystalline structures and their chemical composition onto MTA surfaces after immersion in several conditions. The partial pulpotomy was 88.9% successful, with no significant difference in outcome between deep and extremely deep carious lesions (p = 0.22) or between rapidly and slowly progressing lesions (p = 0.18). Nevertheless, all failed cases were associated with rapidly progressing lesions and extremely deep lesions. All failures occurred when the bleeding time was more than 3 min (p = 0.10). Different crystalline structures were detected on MTA surfaces, with higher calcium percentages in PBS conditions. Within the limitations of the present study, favorable results demonstrated that MTA might be recommended as a suitable agent for partial pulpotomy in permanent molars with irreversible pulpitis. The depth and activity of the carious lesion as well as the bleeding time are important factors in the success of partial pulpotomy treatment. The prolonged bleeding time and the extremely deep rapidly progressing caries could be related with the failure cases in partial pulpotomy treatment of irreversible pulpitis.