The direct endonasal approach performed with the aid of an operating microscope for removal of pituitary tumors has the potential advantage over the traditional sublabial route of minimizing postoperative rhinological complications, yet maintaining a high degree of efficacy and safety. To assess the effectiveness of this procedure, tumor remission rates and surgical complications were documented, and patients' postoperative complaints were recorded using a questionnaire. One hundred consecutive patients underwent 109 endonasal operations for tumor removal. At a median follow-up period of 16 months (range 3-45 months), surgical remission rates were as follows: in 40 patients with endocrine-inactive macroadenomas, 95% for noninvasive and 40% for invasive tumors; in the 20 patients with prolactinomas, 75% for prolactinomas with an initial prolactin (PRL) level lower than 200 ng/ml, 33% for those with a PRL level between 200 and 600 ng/ml, and 0% for those with a PRL level higher than 1400 ng/ml; in the 15 patients with Cushing disease, 73% for microadenomas and 25% for macroadenomas; in the 10 patients with acromegaly, 75% for microadenomas and 50% for macroadenomas; in the five patients with Rathke cleft cysts, 80%; and in the five patients with craniopharyngiomas, 40%. There were seven major surgical complications and no operative deaths. Among the 78 patients who completed questionnaires (response rate 89%), the most common complaints concerned nasal packing (39%), removal of packing (36%), and mouth breathing (35%). At 3 months or longer after surgery, patients quantified sinonasal problems as follows: for facial pain, no problem in 83% and severe difficulty in 4%; for nasal congestion, no problem in 74%, and severe difficulty in 3%; for decreased nasal airflow, no problem in 77% and severe difficulty in 4%; for decreased sense of smell, no problem in 73% and severe difficulty in 4%; and for upper-lip numbness, no problem in 87% and severe difficulty in 1%. Twelve (86%) of 14 patients who had undergone sublabial surgery previously preferred the endonasal approach in terms of pain and ease of recovery. The direct endonasal route for pituitary tumor removal has efficacy and complication rates comparable to those of the sublabial route. Patients generally recover rapidly from this minimally invasive procedure and have no or minimal sinonasal complaints. For patients requiring a repeated operation, the endonasal route appears to be less painful and easier to recover from than the sublabial route. Given the minimal nasal mucosal dissection required and the frequent patient complaints related to nasal packing, use of packing is no longer used for this procedure.