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Introduction Causation of surgical site infection (SSI) following craniotomy is multifactorial. Most preventive strategies (including site preparation and antibiotic prophylaxis) revolve around reducing preoperative contamination of the local site. There is little evidence, however, linking site contamination with postoperative infections. This is important given the preference for performing non-shaved cranial surgery. We undertook a prospective study to document the scalp flora in neurosurgical patients in an Indian setting and to assess possible association with SSI. Materials and Methods A prospective study recruited 45 patients undergoing non-shaved clean craniotomies for various brain tumors. Standard perioperative procedures and antibiotic policy were employed. Prior to and immediately following the pre-surgical scrubbing, we collected swabs and evaluated their growth qualitatively. SSI was documented adhering to CDC guidelines. The association of swab-positivity with various parameters (including SSI) was evaluated. Results Pre-scrub positivity was seen in 18 of 44 patients, three of them developed subsequent SSI. Most were known skin contaminants. Five patients had swab positivity after scrubbing, though none of these developed any SSI. Four of these five had pre-scrub positivity. In three the same organisms persisted (two being Staphylococcus aureus), and one had different growth post-scrub, whereas one patient developed new growth (contaminant mycelial fungus) in the post-scrub swab. We did not find any association between swab positivity and SSI. Swab positivity was also not related to hair-length or hygiene. Conclusion Scalp flora in Indian patients is similar to that described. Pre-surgical preparation does not always eliminate this contamination (especially staphylococcus). However, this does not necessarily translate into increased SSI. Moreover, the results also provide objective evidence to support the performance of non-shaved cranial surgery without an undue risk of SSI.